December 1969 Volume 8, Number 6
INVESTIGATIVE OPHTHALMOLOGY
Light and electron microscopy on plasma cells
and Russell bodies in the iris of a chronic
uveitis patient
Takeo Iwamoto* and Rudolf Witmer
Slit-lamp examination of a 56-year-old woman showed many shiny spots in the iris of her
right eye which had chronic uveitis and complicated cataract. A piece of iris ioas obtained
by iridectomy at the cataract operation and ioas prepared for electron microscopy and studied
with both light and electron microscopes. In the light microscopy of thick (2JM) sections
stained with Giemsa, numerous plasma cells and dense-blue bodies were found in the iris
stroma. The bodies, xohich were identified as the clinical shiny spots, were also intensely
stained with fuchsin, periodic acid-Schiff (PAS), fibrin and Gram stains, indicating that they
were Russell bodies. Electron microscopy revealed that the majority of the plasma cells were
of mature type, icith two forms of rough-swfaced endoplasmic reticulum (RER) and with
cytoplasmic processes and islands. The -flattened cisternae of RER ivere frequently arranged
radially around the Golgi complex, which occasionally reached the cell surface. Single and
-multiple Russell bodies icere contained in the plasma cells. They were various in size and
shape, some being as large as 30 /A in diameter, and always embedded within the RER. The
surrounding cytoplasm was usually intact, with occasional exceptions. "Lipidlike inclusions"
and "dense inclusions" were also seen in the cytoplasm. Plasma cells often surrounded blood
vessels. Although few in number, another type of cell which appeared to be akin to plasma
cells was also found in the iris stroma. The ultrastructure of the above-mentioned cells and
bodies is described, and discussed in relation to their possible functions and cell origin. It
is suggested that the Russell bodies may be produced by a mechanism similar to the block
tohich is assumed to be the cause of "intracisternal granules" in pancreatic exocrine cells.
Key words: iris, Russell bodies, uveitis, electron microscopy,
light microscopy, histopathology, ultrastructure.
_L lasma cell infiltrations in chronic inflammations are a well-known histologic fea-
ture in various tissues. Russell bodies in
the proliferated plasma cells are also common findings in tissues of inflammatory,
as well as of neoplastic, natures. In light
microscopy of the iris, frequent plasma
cell proliferations, often accompanied by
Russell bodies, have been noted in various
pathologic conditions, particularly in nongranulomatous uveitis.1' - This was em-
From the University Eye Clinic, Zurich, Switzerland, and the Department of Ophthalmology,
College of Physicians and Surgeons, Columbia
University, New York, N. Y.
* Reprint requests: Dr. Takeo Iwamoto, Department of Ophthalmology, Columbia University,
630 W. 168th St., New York, N. Y. 10032.
563
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564 hvamoto and Witmer
j;ends see opposite page.
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Investigative Ophthalmology
December 1969
Volume 8
Number 6
phasized recently in relation to the possible function of antibody production in
such plasma cells.3
Electron microscopy of plasma cells of
human and animal tissues in normal and
pathologic states has been made by a
large number of authors,4"27 and the ultrastructure of so-called Russell bodies has
also been reported.7's> 12> 13> 17> 20'21> 2S~30
However, there are still disputable problems to be clarified at an electron microscope (EM) level, such as the origin of
plasma cells and the functional significance
of their structures, including Russell bodies.
In the course of our EM studies of iris
pathology,31 we encountered a patient
whose iris showed many shiny spots in
slit-lamp examination which were identified as Russell bodies by subsequent microscopy. To our knowledge, such large
Russell bodies had not been studied with
the electron microscope. A brief communication on this case was given at the French
Ophthalmology Meeting 1988,32 and the
purpose of this paper is (1) to report in
detail the light and electron microscopy
of the plasma cells and Russell bodies
observed in the iris of this patient and
(2) to discuss some problems raised, on
the basis of our findings and also in comparison with earlier literature.
Case report
The patient, a 56-year-old woman who had
had bilateral chronic uveitis for many years, had
a secondary glaucoma with corneal edema in the
left eye and a complicated cataract in the right
eye. Slit-lamp examination showed the entire
surface of the iris of the right eye to be covered
Microscopy in uveitis 565
with many small shiny spots. With higher magnification these were interpreted as very small
spheres of an unknown birefringent substance.
There were posterior synechiae and a dense,
complicated cataract, but otherwise the anterior
chamber did not show any irritation. The cytologic examination of the anterior chamber fluid
did not give any clues as to the nature of the
tiny spherules; no cells were detectable. A sector iridectomy was performed prior to the intracapsular extraction of the lens of the right eye.
The piece of iris was preserved for EM study.
Material and methods
The material used for the descriptions and illustrations in this paper was confined to the
iridectomized iris of the patient reported above.
However, EM findings on four other irises, which
were also iridectomized at operation, are briefly
mentioned in the Discussion. Several normal human irises obtained by either enucleation or
iridectomy at operation were used as controls
for the electron microscopy.
The iris tissue of our patient was fixed with
4 per cent glutaraldehyde, postfixed with 1 per
cent osmium tetroxide, and embedded in ' Durcupan ACM, following the same method reported
previously.31 Both thick (2 fi) and thin sections
were made with LKB Ultrotome. The 2 /i sections were stained for light microscopy with
Giemsa, PAS, Gram, Weigert's fibrin, and fuchsin stains. All stainings were performed on glass
slides prepared by the same technique as for
Giemsa staining,33 and in each some modifications were made in the usual method; i.e., all
stains were heated (between 80° and 100° C.),
the time in individual steps was shortened, and
all counterstains were omitted. The outlines of
these modified procedures are as follows: Giemsa;
the same as before.33 PAS; 0.5 per cent periodic
acid solution (heated), washing (water), SchifFs
reagent (heated), and washing (water). The
results were similar when pretreated with aniline.31 Fuchsin; Russell's fuchsin solution35
(heated), washing (water), and absolute alcohol.
Fig. 1. Light micrograph of a section of the iridectomized his. Arrows show Russell bodies.
(Giemsa stain; x73). (All the light [Figs. 1 and 2] and electron [Figs. 3 to 181 micrographs illustrated here are from the iris of the patient with chronic iritis that is reported
in the text. The line in each electron micrograph represents one micron unless otherwise
indicated.)
Fig. 2. Light micrographs of variously stained Russell bodies. (A, Fuchsin stain, x440; B,
PAS stain, x440; C, Giemsa stain, x550; D, Gram stain, x550.)
Fig. 3. A low-power electron micrograph of the iris, showing numerous plasma cells (P).
They are located in the stroma (ST); however, those in the anterior border layer (ABL)
are relatively few. AC, Anterior chamber. (x4,500.)
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Investigative Ophthalmology
December 1969
566 hoamoto and Witmer
n
M
Figs. 4 and 5. For legends see opposite page.
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Volume 8
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Similar results were obtained with Ziehl-Neelsen
stain; carbol fuchsin solution (heated), washing
(water), 1 per cent acid alcohol, and washing
(water). Gram; carbol gentian violet (heated),
Lugol's solution, acetone-alcohol, and washing
(water). Fibrin; crystal violet solution30 (heated),
Lugol's solution, aniline xylene, and xylene. Eosin
stain did not produce reliable results in our
tissue.
Thin sections were doubly stained with 2 per
cent uranyl acetate and lead citrate as elsewhere,37 and observed with an electron microscope—EM-9 (Zeiss).
Observations
Light microscopy. Marked changes were
not seen in the pigment epithelium and
dilator muscle layers, when judged from
2 JX sections cut at various dejDths and
stained with Giemsa (Fig. 1). However,
diffuse plasma cell infiltration was observed throughout the iris stroma, including parts of the anterior border layer.
Some plasma cells were around small
blood vessels. Most significant was the
finding of round and variously shaped
bodies stained dense blue with Giemsa
(Figs. 1 and 2C). They were located
among the plasma cells, and easily identified as the same bodies that were observed
as shiny spots in slit-lamp examination.
The bodies stained beautifully with fuchsin
(Fig. 2A). PAS (Fig. 2B), Gram (Fig.
2D), and fibrin stains also produced strongly positive results in these bodies. Their
general morphology, location among plasma cells, and the staining results indicate
that they are Russell bodies (see Discussion ).
Electron microscopy. The pigment epi-
Microscopy in uveitis 567
thelium, dilator muscle, and the superficial layer of the anterior border layer
showed no significant changes, compared
with normal human irises which were
studied as controls. The whole iris stroma,
including parts of the anterior border layer, was occupied by numerous plasma cells
(Fig. 3). Small blood vessels were often
surrounded partly or completely by plasma cells (Figs. 8 and 9), which confirmed
the findings of the light microscopy. However, those plasma cells around the vessel walls were always outside the basement lamina, although a close contact of
the cells with the lamina was observed
in parts (Fig. 9).
The majority of plasma cells were of
a mature type (Figs. 4 and 5). The nuclei
contained highly condensed chromatins in
the periphery, and frequently exhibited a
cartwheel-like pattern (Fig. 4). A nucleolus was also seen in the nucleus (Fig. 4).
The cytoplasm was filled with, rough-surfaced endoplasmic reticulum except where
mitochondria and Golgi complex were located (Figs. 4 to 6 and 9). When observed, the Golgi complex, which consisted of flattened sacs and vesicles, usually occupied the central region adjacent
to the nucleus. However, occasionally a
part of the Golgi area reached the cell
surface (Fig. 6). Centrioles were often
found within the Golgi complex (Fig. 6).
There were two forms of cells with respect to the structure of the rough-surfaced endoplasmic reticulum, one with
long flattened cisteinae (Fig. 4) and the
other with dilated cistemae (Fig. 5) (a
Fig. 4. Plasma cell in the iris stroma. Flattened cisteinae of rough-surfaced endoplasmic
reticulum (er) fill the cytoplasm. They are arranged concentrically around the nucleus (n),
and contain moderately dense material. The chromatin of the nucleus shows a cartwheel-like
pattern, m, Mitochondria; nl, nucleolus. Note many cytoplasmic processes (p); some appear
to have been pinched off, forming isolated small cytoplasmic islands (i). Both the processes
and the islands contain rough-surfaced endoplasmic reticulum. (xl6,200.)
Fig. 5. Plasma cell in the iris stroma. The cisteinae of rough-surfaced endoplasmic reticulum
(a, b) are all dilated, and contain moderately dense material which reveals finely granular
structure in higher magnification (inset). Some cytoplasmic islands (i) possess the same
endoplasmic reticulum as in the cell body, n, Nucleus. (xl6,200.) Inset: High magnification of the portion marked b. (x77,400.)
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568 Iwamoto and Witmer
Figs. (> and 7. For legends see opposite page.
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Investigative Ophthalmology
December 1969
Volume 8
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few cells contained both types). The flattened cisternae of the endoplasmic reticulum were often arranged concentrically
around the nucleus (Fig. 4), while there
were those which showed no regularity.
However, when they surrounded a large
Golgi complex, the orientation was frequently radial (Fig. 6). The cisternae always contained a moderately dense material which revealed a granular structure
in higher magnification (Fig. 5). Many
cytoplasmic processes were seen on the
cell surface, some of which appeared to
be pinched off, forming cytoplasmic islands
(Figs. 4 and 5). Among these typical plasma cells, a different type of cell was sometimes observed (Fig. 7). The nucleus contained a nucleolus, and the chromatin was
not so highly condensed as in the mature
plasma cells. The cytoplasm was characterized by a Golgi complex, an appreciable
number of flattened cisternae of rough-surfaced endoplasmic reticulum, some free
ribosomes, and particularly numerous mitochondria. The cisternae of the endoplasmic
reticulum were usually short and irregularly orientated. However, occasionally they
showed a partial arrangement similar to
that of plasma cells (Fig. 7, arrow). Prominent cytoplasmic processes were also noted.
Single and multiple Russell bodies were
observed in many of the plasma cells (Figs.
10 to 13). They were various in shape
and size, and always located within the
cisternae of rough-surfaced endoplasmic
reticulum (Figs. 10B and 12 to 14). Occasionally several bodies were within one
cisterna (Fig. 12). Those cisternae with
Russell bodies also contained a moderately
Microscopy in uveitis 569
dense material which appeared to be the
same as that seen in the other cisternae
(Figs. 10B, 12, and 13). In general, the
structure of the Russell bodies was dense
and homogeneous (Figs. 10 to 16). However, a wrinkling pattern (Fig. IIF) and
concentric lines (Fig. 16) were seen infrequently in the central region. The surface of the body was usually smooth and
always sharply demarcated from the surrounding medium (Figs. 10 to 12 and 14
to 16). Some large single Russell bodies
appeared to be formed by fusion of several
smaller bodies (Figs. 11A, 11C to E, and
15). Only rarely a body with rugged surface was seen (Fig. 13). Russell bodies
were frequently very large (Fig. 11C to
F); the diameter of some of them amounted
to as much as 30 /x (Fig. HE). Even such
an enormous Russell body was surrounded
by a membrane of rough endoplasmic
reticulum, although the cytoplasm outside the membrane was extremely stretched
—up to the thickness of 40 m/.t (Fig.
14). It was only occasionally observed
that the surrounding cytoplasm was partially disrupted (Fig. 15). However, even
such an uncovered area of the body surface was still sharply delimited (Fig. 15,
arrow). In addition to the Russell bodies,
structures which we tentatively called
"lipidlike inclusions" (Figs. 9, 12, and 18)
and "dense inclusions" (Figs. 6, 9, 17, and
18) were observed in the plasma cell
cytoplasm, including the Golgi area. The
"lipidlike inclusion" consisted of low-density material with a denser rim, and had
no limiting membrane (Fig. 18). The
"dense inclusion" was an aggregation of
Fig. 6. Plasma cell in the iris stroma. A large Golgi complex (g) which consists of flattened
sacs (I) and vesicles (v) occupies the central region of the cytoplasm, and reaches the cell
surface at its lower portion (arrow). A multivesicular body (mv), "dense inclusions" (d), and
two centrioles (c), of which one is very long, are within the Golgi complex. The endoplasmic
reticulum (er) around the Golgi complex is arranged radially. Nucleus is not included in
this section. (xl3,600.)
Fig. 7. A cell occasionally encountered in the iris stroma. n, Nucleus; g, Golgi complex;
er, rough-surfaced endoplasmic reticulum; r, free ribosomes; in, mitochondria. For details,
see text. (xl3,800.)
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570 Iwamoto and Wtimer
Figs. 8 and 9. For legends see opposite page.
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Investigative Ophthalmology
December 1969
Volume 8
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dense granules surrounded by a unit membrane without accompanying ribosomes
(Fig. 17), and was found more frequently
in the Golgi region than in the other
cytoplasmic area. Partial crystalline array
was observed in one dense inclusion (Fig.
18C). A similar dense substance was also
seen in the flattened sacs of the Golgi
complex (Fig. 9). The lipidlike inclusions
were occasionally embedded within the
dense inclusions (Fig. 18B and C).
Discussion
Plasma cell proliferation and Russell
bodies in the iris have been frequent
findings in light microscopy.1"3 The shiny
spots observed clinically in the iris of our
patient were identified as Russell bodies
in plasma cells by subsequent light and
electron microscopy, as discussed below.
These bodies were contained in a relatively small proportion of cells as compared
with the numerous plasma cells which
occupied almost all the iris stroma in the
iridectomized tissue. Since the spots were
seen all over the iris, the plasma cell infiltration in this patient may have been
entirely diffuse throughout the whole iris
stroma.
Most of the plasma cells in the iris
were of the mature type when judged
from their nuclear nature. Their ultrastructure was essentially the same as that reported in various other tissues.17'20> 22 Two
forms of plasma cells had often been observed, and the form with flattened cisternae of rough-surfaced endoplasmic reticulum was said to be an earlier phase than
Microscopy in uveitis 571
that with dilated cisternae.13'17 The flattened cisternae were often arranged concentrically around the nucleus, as seen
elsewhere.10 However, in our study, arrangement in radial orientation was also
frequently noted around the Golgi complex. The Golgi area, which usually occupied the central region of the cell, adjacent to the eccentric nucleus, was sometimes connected directly with the cell surface. Most plasma cells possessed many
cytoplasmic processes, some of which appeared to be pinched off to form small
cytoplasmic islands. Such islands were often found around the cell bodies, and
occasionally formed a large group. Similar
"clasmatosis,"13 "fragmentation,"17' 24 and
"blebbing"20 was also seen by others.
"Dense inclusion" and "lipidlike inclusion,"
as we have tentatively called them, were
frequently seen in the cytoplasm. Similar
(but not identical) structures located mostly in the Golgi complex have been observed
in the plasma cells elsewhere,Si 10> 20 and
other small bodies in the plasma cells, also resembling our "dense inclusions," were
regarded as early forms of mitochondria,18
probable microbodies or lysosomes,20 and
iron particles.20 The true nature of these
"inclusions" is not clear. However, it is
possible that the "dense homogeneous globules" and "dense bodies" observed by
Movat and Fernando20 correspond to our
"dense inclusions" in the Golgi region and
those in the other cytoplasmic area, respectively.
Russell35 was the first to describe in detail the "fuchsin bodies" which were later
Fig. 8. A small blood vessel in the iris stroma. Many plasma cells (p) surround the vessel
wall. L, Lumen of blood vessel; E, endothelium; C, pericyte; B, basal lamina. (x4,600.)
Fig. 9. Higher magnification of a plasma cell which surrounds a small blood vessel (L, lumen;
R, erythrocyte; E, endothelium; B, basal lamina) in the iris stroma. Note that the plasma
cell is located outside the basal lamina (B); the cell is in close contact with the lamina at
the leFt-side surface, but the right-side surface with many cytoplasmic processes (p) is not
covered by the basal lamina. The Golgi complex (g) consists of lamellar sacs and vesicles;
many of the vesicles contain dense material, forming "dense inclusions," and some of the
lamellar sacs also show dense contents (arrow), er, Endoplasmic reticulum; m, mitochondria;
I, lipid-like inclusion. (xl5,300.)
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Fig. 10A. A plasma cell with a large, round Russell body (R). A few lipid-like inclusions (1)
are also seen in the cytoplasm. Small, cytoplasmic processes are on the cell surface. (x5,400.)
Fig. 10B. Higher magnification of a portion (a) in Fig. 10A. Many long, flattened profiles of
rough-surfaced endoplasmic reticulum (er) and a few mitochondria (m), which are characteristic of plasma cells, can be seen in the cytoplasm. Russell body (R) is homogeneously dense,
and has a sharply demarcated, smooth surface. The body is completely surrounded by a membrane studded with ribosomes (arrow), and between the membrane and the Russell body
there is a thin layer of moderately dense material which appears identical with that contained
in the other cisternae of rough endoplasmic reticulum. (x25,000.)
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Fig. 11. Russell bodies with various sizes and shapes. A to F are all shown at the same
magnification. (x2,900.) Some density patterns seen in C, D, and E are artifacts. In B a
plasma cell contains multiple small Russell bodies, and in the others either a huge, round
Russell body (F) or single but irregularly shaped Russell bodies are seen. Those bodies with
irregular shapes (A, C, D, and E) appear to have been produced by confluence of two to
several round Russell bodies. The nucleus (n) of the plasma cell containing a Russell body is
visible in A. In E the maximum diameter (from arrow to arrow) of the Russell body amounts
to as much as 30 p. A wrinkling pattern is observed in the central region (r) of the body in
F; whether this is an artifact or not is not clear. Portions marked with a, b, and c are magnified in Figs. 16, 15, and 14, respectively. (x2.900.)
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574 Iwamoto and Witmer
Iiwestigative Ophthalmology
December 1969
^•i
12
Figs. 12 and 13. For legends see opposite page.
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called Russell bodies. Subsequent histochemical studies showed that these bodies
were probably muco- or glycoprotein.47"49
There may still remain some arguments
as to whether all the structures reported
under various terms, such as "Mott cell,"
i7, so "g r a p e cell,"51 and "plasma cell droplet" stained blue with Giemsa,52 are essentially the same element as Russell
bodies.21'53'54 In our material, which was
prepared originally for electron microscopy, eosin staining was not successful—
probably because of the different fixation
and embedding. However, our bodies,
which stained dense blue with Giemsa,
were well in accord with those commonly
referred to as Russell bodies in their
microscopic structure and other staining
properties; i.e., they were intensely positive in PAS,47"40 Gram,49 fibrin,8 and fuchsin35 staining. Electron microscope studies
on so-called Russell bodies were also reported in various tissues as mentioned,
and the ultrastructure of our bodies was
very similar to that of those by other workers,8' 13> 20> 21> 2S> 20 although these earlier
reports did not include such large, single
Russell bodies as we saw in the iris. In
our study, essential ultrastructural differences were not found between large single
bodies and the smaller multiple bodies, of
which the latter may correspond to those
which constitute "Mott cells."13-1T Some
authors stated that, in multiple myeloma
and macroglobulinemia, dense spherules
resembling Russell bodies could be seen
Microscopy in uveitis 575
in the nuclei of plasma cells,30'S5 but we
never encountered them in our tissue.
The origin of plasma cells is still obscure; various cells have been presumed to
be precursors, e.g., the reticulum cell and
its possible derivatives, including the hemocytoblast,13' -3; 3S"43 lymphocyte,41'44 macrophage,41 and perivascular adventitial
cell.43'4G The fact that we saw many plasma
cells surrounding the iris blood vessels
seems to support their adventitial origin.4540
However, they were always located outside the basement lamina, and no cells
which clearly indicated transition from
pericytes to plasma cells were seen in our
study. Among the numerous plasma cells in
the stroma, we encountered some cells such
as those shown in Fig. 7, which were not
seen in our normal control irises. It is not
clear to which category they belong, but
they appeared similar to one of the cells
observed in plasmocytic myeloma.10
Cells with well-developed, rough-surfaced endoplasmie reticulum, such as plasma cells, pancreatic cells, and other gland
cells, are believed to be concerned with
protein production.17'5G> 57 In addition,
many findings have strongly suggested a
probable function of the plasma cell as
a producer of antibody or gamma globulin,17- 22> 43> 44> 4G> 5S>59 although there are
questions of how the antigenic informations enter the cell.22-G0 A possibility that
Russell bodies contain gamma globulin
or antibody has also been suggested.22'4S>G1
Some crystalline structures were observed
Fig. 12. A plasma cell with several relatively small round Russell bodies. All the bodies are
within the cisternae of rough-surfaced endoplasmie reticulum. Three bodies (a, b, and c) are
contained in one cisterna. Dilated cisternae of endoplasmie reticulum (er) fill the rest of the
cytoplasm, and a few empty vacuoles (v) are also visible near the cell surface. Whether or not
such vacuoles resulted from discharge of the contents of the cisterns is not clear; those vacuoles were observed only rarely. In the cytoplasm a lipidlike inclusion (I) is also seen, and
its upper portion appears to be uncovered. (xl3,500.)
Fig. 13. A Russell body (R) with rugged surface. It is conceivable that this minute irregularity of the body surface resulted from fusion of numerous smaller Russell bodies. In this
high magnification the Russell body itself appears to be composed of extremely fine grains
(ca. 30 A.); however, the value of describing such fine graunlarity in detail may be questionable, because this could be caused by the embedding plastic07 or other artifacts.cs
(x52,200.)
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576 Iwamoto and Witmer
Figs. 14 to 16. For legends see opposite page.
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December 1969
Microscopy in uveitis 577
Volume 8
Number 6
within plasma cells in other tissues.s>12> 13>
17,20 Although we did not see such crystals
in our cells, a somewhat similar crystalline
array was found in one "dense inclusion."
The mechanism of presumed secretion
and excretion of the above substances in
plasma cells is quite obscure, and the following discussion concerning this subject
includes some hypotheses. Recent studies
of pancreatic exocrine cells seem to strongly support the view that the proteins synthesized at the ribosomes are transported
through the rough-surfaced endoplasmic
reticulum to the Golgi complex, where
they are condensed and finally excreted.
57, C2, G3 Since, as has b e e n known, 1 ' 1 ' 17>
23
the structural elements, particularly the
endoplasmic reticulum of the plasma cells,
resemble those of the pancreatic exocrine
cells,02- G'J> G5 it is conceivable that the same
mechanism as in exocrine cells may be applicable to plasma cells. If so, one possible
interpretation is that the moderately dense
material observed in the cisternae of rough
endoplasmic reticulum, which may represent proteins, is carried to the Golgi area
and condensed to form "dense inclusions,"
as a somewhat similar possibility had been
presumed.20 Actually, the dense inclusions
were most often seen in the Golgi region.
In addition, some of them appeared to be
moving toward the cell surface (Fig. 17B);
this was reminiscent of the movement of
zymogen granules in the pancreatic cells.
However, no pictures indicating their excretion out of the cells were obtained. A
similarity between Russell bodies and
"dense homogeneous globules," the latter
of which might correspond to our "dense
inclusions" in the Golgi region, has been
pointed out, and a close relation in their
occurrences has also been suggested.20
However, our "dense inclusions" so far
studied possessed a granular structure,
which was common to those in both the
Golgi complex and the other cytoplasmic
area, and were always surrounded by
limiting membranes with no accompanying ribosomes, whereas the homogeneously dense Russell bodies were always encircled by ribosome-studded membranes.
No clear transition between the two structures has been seen, although it was noted
that the grade of condensation of the
granular substances in the "dense inclusions" was not constant, some appearing
more condensed than others (Figs. 17C
and D and 18B and C). Some authors
thought that Russell bodies were produced
by direct condensation of the moderately
dense cisternal material.12-13> 20 As to how
the Russell bodies are produced, our EM
findings on the other four human irises
seem to warrant a brief description. An
Fig. 14. Higher magnification of a portion (c) in Fig. 11F. Even such an enormous Russell
body as this (R) is surrounded by the membrane of rough endoplasmic reticulum. The cytoplasm is extremely thinned—up to ca. 40 m/t (arrow)—and yet it retains an intact structure.
(xl9,200.)
Fig. 15. Higher magnification of a portion corresponding to (b) in Fig. 11D; the picture
was taken from an adjacent section. Although the membrane of rough endoplasmic reticulum
surrounding Russell body (R) is relatively well retained, the other cytoplasmic elements
illustrated here seem to have largely degenerated, and at the portion on the left (arrow) the
body has lost it cytoplasmic cover entirely. Another well-preserved plasma cell (P) is seen on
the right. It is also shown in this picture that two different curves constituting a Russell body
surface meet at one point, as if the two curves crossed without being influenced by each other.
Note however that the fine structure of the Russell body inside the surface line is not
changed at all even at this angular area (*); it is homogeneous and dense as in other parts.
(xl9,200.)
Fig. 16. Higher magnification of a portion (a) in Fig. 11 A. This particular Russell body has
narrow, less dense circular zones in the central area. Two such rings are arranged concentrically (arrows). A thin cytoplasm covers the Russell body surface on the left. (xl5,900.)
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578 hoamoto and Witmer
Figs. 17 and 18. For legends see opposite page.
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lnvestigatioe Ophthalmology
December 1969
Volume 8
Number 6
appreciable degree of plasma cell infiltration was seen in three of them; two had
a possible herpetic infection, and one was
from a heterochromic cyclitis. Many of
these plasma cells contained "dense inclusions" but no Russell bodies. The last patient was being treated for glaucoma, but
the iris appeared normal clinically. A
small number of plasma cells, however,
were observed in this iris, and most of
them possessed large Russell bodies identical with those reported in this paper. These
few experiences appear to coincide with
a light microscopic rinding in other tissues,
in which the occurrence and number of
Russell bodies were not dependent upon
the number and density of plasma cells.49
These also seem to be compatible with
an assumption that Russell bodies are
products of some unusual functional condition of the plasma cells.8'49 Again, in
the pancreatic exocrine cells, so-called "intracisternal granules," which could be compared to the Russell bodies in the plasma
cells, were presumed to be the result of
a block during the course of protein trans-
Microscopy in uveitis 579
portation from the rough endoplasmic
reticulum to the Golgi complex.00 It is very
tempting to assume that Russell bodies
may be produced by a mechanism which
is similar to the block in the pancreatic
exocrine cells. In experimental animals Russell bodies occurred when a specific antigenic stimulus was given.4S Plasma cells
with Russell bodies were often regarded
as a degenerative phenomenon by earlier
histologists.49 In our study the cells themselves usually appeared intact, even when
the included Russell bodies were enormously large; this confirms other findings.13' 29 Apparently degenerated changes
of those cells were observed only occasionally and partially, allowing an interpretation that this probably resulted from too
much expansion of the included bodies.
Even in such portions where the Russell
bodies were uncovered, the bodies retained
their unchanged structure with sharply
demarcated surfaces, and the possibility
that the Russell bodies might be dissolved
out to the surrounding medium seemed
unlikely. No signs indicating that the
Fig. 17. A, B, C, and D are all parts of the plasma cells found in the iris stroma,
and show "dense inclusion." A: Several "dense inclusions" (d) are observed in the periphery
of the Golgi complex (g). Each is surrounded by a single smooth-surfaced membrane, er,
Rough-surfaced endoplasmic reticulum. (xl7,400.) B: "Dense inclusions" (d) are arranged
in a row, between arrays of dilated cisternae of rough-surfaced endoplasmic reticulum. The
rows of both the cisternae and inclusions are oriented nearly radially, as if the dense inclusions are passing from the central Golgi area (g) to the cell periphery, c, Centriole within
the Golgi complex. (xl7,400.) C: Higher magnification of a region of the Golgi complex in
a plasma cell, showing a "dense inclusion" (d). The inclusion is composed of dense, granular
material and is surrounded by a triple-layered unit membrane (arrow). (x77,400.) D: Higher
magnification of the cytoplasm of a plasma cell, showing a Russell body (R) and a "dense
inclusion" (d). In this high magnification the Russell body seems to consist of extremely fine
grains (see the explanation of Fig. 13). The "dense inclusion" is clearly composed of larger,
dense granules (ca. 100 A.). The limiting membrane of the inclusion is not visible at the
lower portion, probably due to tangential sectioning; in this region the constituent dense
granules appear to be arranged in parallel rows (arrow). (x77,400.)
Fig. 18. A, B, and C are all parts of the plasma cells in the iris stroma, and show "lipidlike
inclusions." A: A lipidlike inclusion (I) in the cytoplasm of a plasma cell. It is of low density
and homogeneous, except for the denser peripheral zone, and has no limiting membrane.
(x54,000.) B: Two lipidlike inclusions (I) are embedded within the dense granular material
(d) of a "dense inclusion" which has a limiting membrane (arrow). (x54,000.) C: A lipidlike
inclusion (I) embedded within a "dense inclusion" (d). Dense parallel lines ca. 200 A. apart
are clearly seen within the dense inclusion (arrow); between the dense lines there are thinner, less dense, intermediate lines. These lines may have been caused by a crystalline array
of the constituent particles of the dense inclusion. (x54,000.)
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Investigative Ophthalmology
December 1969
580 huamoto and Witmer
moderately dense contents of the rough
endoplasmic reticulum are directly excreted
from the cells have been seen, except for
a few plasma cells which we interpreted
to be artifact. Thus, in our study, no clear
sign of excretion of the plasma cell contents has been obtained, with one doubtful exception of lipidlike inclusion (Fig.
12). However, while there is an assumption that the cytoplasmic processes or
"villi" on the plasma cell surface could be
concerned with uptake of substances,20 it
seems more likely that the above-mentioned cytoplasmic islands, which usually
contained cisternae of rough endoplasmic
reticulum, may be concerned with excretion, as has been postulated.13'2G The unresolved problems discussed above remain
to be clarified by future study.
The authors wish to thank the Elektronenmikroskopischen Zentrallaboratorium der Universitat
Zurich for affording facilities to use the Zeiss
electron microscope EM-9.
10.
11.
12.
13.
14.
15.
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