From www.bloodjournal.org by guest on July 31, 2017. For personal use only.
Human
IgA1 Half-Molecules:
Clinical
Immunologic
Features
in a Patient
With
Multiple
Myeloma
By Ikunosuke
Abnormal
IgA,
one
and
heavy
Sakurabayashi,
half-molecules
one
light
Kohjin
consisting
chain
were
of
found
Kin,
and
Tadashi
in its Fc portion.
in a
and
light
and
Kawai
We suggest
chains
were
that
its heavy
probably
bound
patient (N.N.) with typical multiple myeloma.
The serum and the urine of this patient
contained
both 7.OS and 3.9S IgA myeloma
proteins.
The lgA half-molecules
(3.9S) were
found to have a molecular
weight of 59,000
daltons and were composed
of one a, chain
noncovalently,
since
the interchains
connecting the heavy and light chains of these
IgA half-molecules
were easily dissociated
with 1% SDS and 8 M urea. Cytologic
studies
identified
at least two types of myeloma
cells, and it is possible
that half-molecule
IgA
of about
production
of
40,000
22,000
daltons
daltons.
and
degradation
suggested
the N.N. half-molecules
M
one
light
Furthermore,
chain
enzymatic
the
Ihat the a chain
of
had a large deletion
OST
PATIENTS
with
typical
monoclonal
immunoglobulins,
structure
of these
include
malities
proteins,’
and
Half-molecule
half-molecule
immunoglobulin
reported
ofa half-molecule
in experimentally
induced
globulin
with
of lgG-K
extramedullary
detected
type
four
multiple
myeloma
carry
and recently
abnormalities
and
age
of 47
increasing
pain
From
types
of
molecular
by
Potter
and
Kuff,2
who
chain and one
half-molecule
light chain
immuno-
and Jacobs3
such patients
in a patient
have been
IgA
yr.
and
and
of
February
in part
Ministry
Vol.
shoulder
female,
been
suffered
and
reprint
exposed
was
hospitalized
to radiation
a second-degree
regions
again
She
Pathology.
24, 1978;
accepted
requests
and
No.
Jichi
& Stratton,
to Ikunosuke
2 (February),
Inc.
1979
October
Grant
Welfare.
Minamikawachi-machi,
by Grune
53,
Clinical
by a Research
of Health
School,
/979
had
Japanese
had
myeloma,
this
burn
on
at the end
was
in 1974
from
the
her
forehead.
of I 975,
readmitted
because
atomic
bomb
She
complained
time
she was
at which
to the
of lumbago,
in Nagasaki
hospital
of
found
in mid-January
of
Medical
School.
Minamikawachi-machi,
Kawa-
Japan.
Supported
Address
She
with IgA
IgA.
REPORT
hypergammaglobulinemia.
Department
Submitted
Medical
she
lumbar
Tochigi-ken.
Bureau,
a 78-yr-old
pain.
in a patient
of half-molecule
Fishkin,t
have had
year.
the
chi-gun.
N.N.,
shoulder
in the
proteinuria
following
Blood.
various
in the
were first described
by Spiegelberg
and
reported
later.9’2
Because
the authors’2
to study
half-molecule
the structural
abnormality
Patient
History.
hypertension,
c:
among
whole-molecule
been reported.
These
abnor(2)
incomplete
myeloma
IgA consisting
ofone
a heavy
myeloma
in mice.
Abnormal
CASE
the
have
proteins,
immunoglobulins.
was first described
in humans
cases were
additional
the opportunity
report
will treat
to have
mutation
subsequently.4
while
the
from
producing
was reported
first in man by Hobbs
soft-tissue
plasmacytoma.
Four more
IgA half-molecules
at
result
cells
IgA.
monoclonal
immunoglobulins
( I ) heavy-chain
disease
(3)
might
myeloma
from
6. /978.
the
Intractable
Diseases
Division.
Public
Health
Japan.
Sakurabayashi,
Kawachi-gun.
M.D.,
Tochigi-ken.
Dept.
of
Japan.
Clinical
Pathology.
Jichi
329-04.
0006-4971/79/5302-0013$01.00/0
269
From www.bloodjournal.org by guest on July 31, 2017. For personal use only.
270
SAKURABAYASHI,
Physical
examination.
Significant
mass
findings
at the
region.
Patient
included
right
tibia.
Scattered
There
rhonchi
was
were
normal. The
liver
was
palpable
consistency,
and
the
spleen
hypertensive
retinopathy
blood
pressure
N.N.
was
a 3 X 5 cm
also
over
was
170/86
also
mm
both
right
(one
of the
palpable
fields,
right
remainder
was
physical
a 7 X 5 cm
around
margin,
the
of firm
up
and
was
was
and
turned
examination
ileocecal
dullness
smooth
76 beats/mm
KAWAI
housewife.
and
of cardiac
Fundoscopy
rate
of the
area
costal
flngerbreadth).
Heart
mass
the
AND
emaciated
clavicle
nonpainful
although
the
classification).
The
although
end
beneath
palpable
Hg.
developed
sternal
lung
fingerbreadths
(Keith-Wegener
was
at the
a 3 X 3 X 3 cm
audible
three
a normally
mass
KIN.
stage-Il
regular,
and
within
normal
limits.
Laboratory
I . I %, and
count
metamyelocytes,
6%
4%
eosinophils,
a monoclonal
creatinine
was
cells.
Conversely,
below
normal
was 9.0 g/dl,
white
band
and
showed
revealed
Hemoglobin
data.
reticulocyte
cell
neutrophils,
2%
mg/dI.
Serum
the
Bence
osteolytic
protein
well
as
punched-out
lesions
the
was
in the
count
9.4
and
presence
28.2
of 56%
and
l04/cu
45%
lymphocytes,
I%
electrophoresis
mg/dI,
and
serum
pleomorphic
plasma
series,
of the
radius,
mm,
revealed
granulopoietic
survey
humeri,
X
count
serum
was
X-ray
bilateral
the
nitrogen
present.
cell
monocytes,
g/dI,
the
286
white
erythropoietic
also
skull,
cell
7%
urea
revealed
proteinunia
red
differential
was
Blood
aspiration
as
Jones
The
neutrophils,
to 43.1%.
marrow
megakaryocytes,
limits.
total
27%,
mm.
segmented
amounting
Bone
hematocnit
3200/cu
34%
basophils.
-y, fraction
5.3
count
ulna,
were
skeletal
femur,
system
tibia,
and
fibula.
Hospital
The patient
course.
cyclophosphamide
200-mI
(Endoxan)
blood
Although
transfusions.
bone
of gradual
pain
was treated
every
other
for multiple
day,
and
Trichloromethiazide
at the
right
clavicle
and
right
tibia
proteins
and
concentrated
electrophoresis
Williams),
immunogel
Half-molecule
chromatography
X
cm),
80
IgA
buffer,
filtration
(Sephadex
was
and
Denmark)
according
in cold
incubating
at
Sepharose
3.0.
by
S2,,w value,
and
the
Cytologic
cence
patient’s
I 00 mg
infusions
for
hospital
technique
24
and
hypertension.
course
was
on the
studies
(FITC
pH
After
was
eluted
a glass
applied
protein
that
was
column.
neutralized
gel
electrophoresis
(60#{176}C) as
of Porter,’8
isolated
of the
and
lgA
bone
M
X
mm)
50
lgA
and
was
determined
by the
and
by
Centniscan
using
the
method
4B
was
coupled
by
pretreated
M glycine-HCI
weight
sodium
England)
to give
short-column
and
0.2
1.0%
75,
procedure’t
Calvanico
the
Molecular
containing
M
were
with
with
concentrated.
0.75
Chemicals)
Sepharose
filled
eluted
size
Copenhagen,
(rabbit)
was
gel
(column
Fine
CNBr-activated
antibodies
(MSE
digestion
G-200
M NaCI
using
an
was
dodecyl
a u.v.
extrapolated
method.
monoiodoacetamide,’6
Tomasi,’7
high-
papain
of Nisonoff
and
digestion
Wissler’t
were
half-molecules.
marrow
labeled),
is,
mercaptoethanol
pepsin
of Sephadex
(Pharmacia
anti-a
a standard
described
immunodiffusion.
0.15
4B
(PAGE)
using
was
0.75
containing
The
ultracentnifugation
equilibrium
digestion
(15
then
determined
8.6,
That
to the
cellulose
(Grabar-
(DAKO-immunoglobulins,
to which
column
radial
by means
Sepharose
was
as by analytical
with
8.0)
single
urine
antiserum
procedures:
immunoelectrophoresis
and
at pH
Cuatrecasas.’3
(0.2M,
hr.
alkylation
method
of
chain
following
gel
and
serum
buffer
the
agar
superfine),
patient’s
anti-a
method
buffer
sedimentation
trypsin
performed
the
Sedimentation
and
temperature
also
administered
the
using
0.07),
(CNBr)-activated
with
polyacrylamide
as well
filter.
employing
The
7.5%
(SDS),’4
nm)
Reduction
to
172
G-200
the
bromide
I ml of sample
pH
determined
(280
also
and
‘y globulin
METHODS
analyzed
8.6,
M Tris-HCI
coupled
borate
were
pH
from
a 0.1
cyanogen
4#{176}C
for
4B,
at
isolated
employing
suspended
sulfate
was
continued,
AND
urine
(barbital
affinity chromatography
buffer
I 0 mg prednisone
occasional
improvement.
Serum
2.5
with
administered
(Fluitran)
MATERIALS
acetate
myeloma
was
and
were
electron
carried
out
using
Wright-Giemsa
stain,
immunofluores-
microscopy.
RESULTS
Cellulose
monoclonal
also showed
IgA-X type
and
urine
acetate
electrophoresis
band in the ‘y, region,
of the
amounting
a well-defined
band in the
monoclonal
immunoglobulin
showed
two distinct
precipitin
N.N.
serum
to about
showed
a relatively
4 g/dl.
The urinary
“y, region.
Immunoelectrophoresis
and A Bence Jones protein
arcs
of identical
mobility
broad
pattern
(Fig.
revealed
1.). Serum
against
the anti-a
From www.bloodjournal.org by guest on July 31, 2017. For personal use only.
HUMAN
IgA,
HALFMOLECULES
271
AWH$
__________
vps
A
AlgA
A-K’
PS
A
AL
AlgA
“Pu
Fig.
serum
urine
(B).
N.N.
serum
shows
double
arcs
against
anti-a
antiserum
having
the
same mobility
(arrow).
PS, N.N. serum;
Pu,
N.N.
urine;
AWHS,
anti-whole
serum;
A.lgA, anti-a
A.K., anti-c antiserum;
A
A K
Immunoelectrophoresls
of
(A) and 30-fold concentrated
1.
NitI.
t
A- i
human
B
chain antiserum;
A.L., antl-X anti-
PU
serum.
antiserum.
In the immunogel
filtration
examinations,
consist
of two different
components,
larger
(‘-7S)
that formed
a spur against
the anti-a
antiserum
diffusion
The
two
using anti-a
serum
control
N.N.
reacted
IgA
molecules
monoclonal
M
.
IgA
AWH&
antiserum
IgA
.
was
produced
against
and
anti-a,
failed
only
as belonging
G
a single
antiserum
to react
identified
and
(Fig.
IgA molecules
were found to
smaller
(-5S)
molecules
2). Single
radial
immunoprecipitin
showed
against
ring.
a partial
anti-a,
to the subclass
antiserum.
identity
Thus
with
the
IgA,.
A
..--..
AlgA
A
V
A
-
t_
Fig.
2.
lmmunogel
filtration
pattern
of N.N. serum. N.N. serum shows two
arcs with a partial Identity against anti-a
chain
antiserum
(arrow), representing
the IgA half-molecules
and the larger IgA
molecules
(-iS);
a small amount
of X
Bence Jones protein is also seen.
From www.bloodjournal.org by guest on July 31, 2017. For personal use only.
SAKURABAVASHI,
272
E
KIN,
AND
KAWAI
1.
0
(5
a,
SI ‘I
U
C
(5
.0
/
S
S
,1
0
-a
4
20
10
30
40
Tube
50
60
Number
FIg.
3.
Elution pattern on NN serum (-)
and urine (- - -) on Sephadex
G-200 column
Solvent was lris-HCI buffer (pH 8.0). Half-molecule IgA was eluted at tube No. 34-42.
(‘-.).
The
low molecular
Sephadex
G-200
tography
coupled.
weight
column
IgA
was
chromatography
employing
CNBr-activated
This produced
a single
ultracentrifugation,
the abnormal
protein
peak with a sedimentation
rium
of 59,000
daltons,
standing
band
isolated
from
(Fig.
Sepharose
on 7.5%
the N.N.
3) and
purified
4B to which
PAGE
(Fig.
serum
chromatography.
and
urine
by affinity
anti-a
5A).
using
chroma-
antiserum
was
On analytical
low molecular
weight
IgA showed
constant
of 3.95 and a sedimentation
in sharp
contrast
to the I 55,000
daltons
a single
equilibfor the
1.0
E
C
0.8
0
Co
0.6
C
0
U
C
LU
0.4
0.2
MU.
EngI.nd
0
Rdius
Fig.
4.
Ultracentrifugal
analysis
of sedimentation
velocity
(S,,)
of the purified
half-molecule
IgA
isolated
from N.N. urine by CNBr-activated
affinity chromatography
(conjugated
anti-a
chain antiserum).
Ultraviolet
pattern at 280 nm was taken at 10-mm intervals
after reaching the maximum
speed (50,000
rpm,
200,000
G) by using a single-sector
cell (Centrlscan
75, MSE, England).
From www.bloodjournal.org by guest on July 31, 2017. For personal use only.
HUMAN
IgA,
Fig.
5.
phoresis
HALFMOLECULES
Polyacrylamlde
of the purified
273
gel electroIgA half-mole-
cule
In 1% sodium dodecyl
sulfate and
urea. (A) Unreduced
3.95 IgA without SDS and 8 M urea, (B) 3.95 IgA with
1% SDS, (C) reduced
IgA half-molecule,
and (D) reduction
by heating (60’C) after
Incubation
of 1% SDS and 8 M urea. IgA
half-molecules
easily
dissociated
Into
heavy and light chains. The top protein
band of B and C shows
intact
halfmolecule
IgA. The second
protein band
of C and D shows
a chains
(40,000
daltons),
and third protein band of C and
D shows
> chains
(20,000
daltons).
8
M
whole-molecule
and
alkylated
IgA
purified
of this
low
patient
molecular
(Fig.
4). The
weight
IgA
molecular
was
estimated
weight
of the
by SDS
reduced
PAGE
to
be around
40,000
daltons
for the a chain
and 22,000
daltons
for the A chain,
compared
to 56,000
and 23,000
daltons,
respectively,
for the whole-molecule
IgA
(Fig. 5C). These were more susceptible
to reduction
and alkylation
than the control
IgA myeloma
proteins,
and they readily
dissociated
into a A chain
and an a chain
upon
being
(Fig.
5D).
FIg. 6.
antIserum,
incubated
Following
at 60#{176}C
for 30 mm in the presence
of 1% SDS
papain
digestion,
the molecular
weight
of Fab
and 8 M urea
portion
of the
Immunofluorescent
micrograph
of N.N. myeloma
cells after incubatIon
wIth anti-a
showing many strongly stained cells and smaller faintly stained cells (arrows).
X 1000.
chain
From www.bloodjournal.org by guest on July 31, 2017. For personal use only.
274
SAKURABAYASHI,
Fig.
7.
well-developed
:: 10,000.
low
IgA was -37,000
failed to show the
weight
antigenetically
Immunofluorescent
FITC-labeled
KAWAI
study
anti-a
of the
antiserum,
N.N.
daltons,
and its high temperature
trypsinFc fragment
or its equivalent
portion.
myeloma
cells
demonstrated
two
producing
cells: the major
cells showed
minor cells a faint orange-green
discolored
Electron
microscopy
of the myeloma
a typical
staining
cells also
the
ribosomes,
and
cells
AND
Electron
micrograph
of N.N. myeloma
cells showing
two types of cells, a larger cell with
endoplasmic
reticulum
and a smaller cell with poorly developed
endoplasmic
reticulum.
molecular
olysis
KIN,
major
focally
showing
cells
showing
dilated
poorly
well-developed
in the
distinct
bone
marrow,
strong
green
staining
(Fig. 6).
revealed
two distinct
mitochondria,
rough-surfaced
endoplasmic
reticula,
developed
endoplasmic
reticula
and
using
populations
Golgi
of
IgA-
and
cell
the
types,
apparatus
and the smaller,
ribosomes
(Fig. 7).
minor
DISCUSSION
IgA half-molecules
appear
to be a very rare type of monoclonal
immunoglobulins
protein).
To our knowledge,
such immunoglobulins
have been found
in only
four
other
patients,
two of whom
suffered
from classical
multiple
myelomat9
one
(M
from plasma
cell
Half-molecule
Fishkin,t
who
molecular
weight
leukemia,’#{176} and
IgA in human
showed
of 46,500
fragment.
A case
who also presented
weight
of 45,000
half-molecule
that
the
one possibly
from pulmonary
myeloma
was first described
heavy
daltons
and
chain
that
of
it was
the
tuberculosis.”
by Spiegelberg
half-molecule
antigenically
IgA
deficient
and
had
a
of the
Fc
of plasma
cell leukemia
was described
by Bernier
and Berman,’#{176}
the heavy
chain
of half-molecule
IgA as having
a molecular
daltons.
Biewenga
and
Ban
Loghemt
described
a case
of
IgA-producing
multiple
myeloma
in which
the
molecular
weight
of
From www.bloodjournal.org by guest on July 31, 2017. For personal use only.
HUMAN
IgA,
HALFMOLECULES
heavy
its
chain
molecular
was
deletion
275
determined
in the
to be 45,000
DNA
coding
daltons
for this
alternatively,
case
that a rapid intracellular
degradation
half-molecule
IgA was investigated
by
of
SDS-PAGE,
determined
the
molecular
and
portion
weight
suggested
of the chain
mechanism
Kang
and
that
had
existed.
Shim,”
of its a chain
either
a
occurred
The
who,
or,
fourth
using
to be 53,000
daltons
and suggested
the absence
of the hinge region
in the abnormal
molecule.
chain of half-molecule
IgA (N.N.)
in case described
here was significantly
The
heavy
smaller
than
of
human
that
of
the four-chain
IgA reported
half-molecule
These
findings
agree
ultracentrifugation,
plasma
cell tumor
and
the
heavy
IgA (N.N.).
The
so far are summarized
with
the
chain
from
form
6C protein,
have
46,000
IgG
the carboxyl
have involved
an interchain
Our data
IgA (N.N.)
whole-molecule
disulfide
deletion
who,
using
analytical
in experimentally
IgA molecule,
68,000
daltons,
described
in contrast
by Spiegelberg
terminus
of its -y chain
half-cystine
residues
with
the
induced
daltons,
ordinary
and
Heath,22
it was
was probably
intact
and that the
in the CH3 domain
that normally
bond.
indicate
that the molecular
is about
14,000
daltons
IgA (N.N.)
and that,
a large
Mushinski,2#{176}
data
was determined
to be 54,000
daltons.
Seki and Appella2’
the two-chain
IgA molecules
(47A),
63,000
daltons,
and the
protein,
40,000
daltons,
in contrast
with 6A heavy
chain,
55,000
daltons.
In a case of half-molecule
that
might
of
determined
molecular
weights
in mice as follows:
the two-chain
6A heavy
chain,
which
published
similar
data:
heavy
chain
from 47A
suggested
deletion
data
physicochemical
in Table
I.
in the
weight
for the heavy chain of half-molecule
smaller
than
that of the heavy
chain
from
antigenically,
the smaller
a chain appears
to
Fe fragment.
The
apparent
deletion
is assumed
to be
localized
in the CH3 domain,
since a deletion
of about
14,000
daltons
is almost
equivalent
to the size of the CH3 domain
and would
seem to be a likely cause
of a
lack of four-chain
molecule
formation.
Although
Bernier
and co-workers’#{176} 23 established
the fact that the light-heavy
disulfide
bond
light-heavy
the protein
Regarding
results
were
of half-molecule
IgA
interchain
bond
easily dissociated
the
biologic
described
activity
bound
the
The
to bind
guinea
to complements
types.
It was suggested
that
Fe fragment
responsible
was
present,
of half-molecule
by Spiegelberg:24
form a complex
with Clq and failed
neutrophils,
or monocytes
or to
half-molecule
protein
corresponding
by experimentally
IgA secreted
and we suggest
to
the
minor
indicate
as well
as to each
cells
the
the
as
following
failed
to
of human
lymphocytes,
while
the aggregated
of the above-mentioned
did not
activities.
lack
all the
cell
structures
on
IgA, myeloma
protein
was formed
by an
evolved
during
the malignant
transformation
producing
by patient
that
that
inasmuch
half-molecule
the Fe receptors
pig mast
cells,
of the plasma
cells or was an aberrant
form
of an
component
of the normal
genome.8
In fact, the high
heavy chain,
data
immunoglobulins,
unaggregated
these half-molecules
for these biologic
It is suggested
that the half-molecule
IgA, mutant
clone of cells that either
demonstrated
Half-molecule
our
of the half-molecule
IgA is noncovalent,
in 1% SDS and 8 M urea.
one
of two
of
mouse
N.N.
myeloma
cells had
abnormal
discolored
IgA,
line
frequency
plasma
fluorescence
that existed
of mutation
cell lines.25
a large
deletion
cells
with
lines,
their
as a
was
of
probably
scanty
its
From www.bloodjournal.org by guest on July 31, 2017. For personal use only.
276
SAKURABAYASHI,
C’)
C4
0
-‘
,-
_c
5-
C,.
-.g
8o
a
O
0
Es’
E’D
#{149}0
,
#{149}#{149}
0
,
-o
.2a)
0
s..CO
0M)
0
0
8
5u
_D
0
E
,
:
z
0
C
C
.!
3
E
-
4
i4’
0.
1
.E
‘IF
as
:
3
-
V
0o
#{176}.
-5
-
.E
...
.2
e.2g
0
;u
‘I
,g
‘
U-
LS
L
.C
:
C
..05
0
._-
8,
g
C’)
C1
(‘.4
C”
‘6
-5
C
.E’
a
0
-
-C
S
a
2CO
0,.
0
a
.!o,
in
‘O
C’)
‘
E
a
LI,
0
g
0
-=
‘
o
0
0S
.C
0
V
C
0
Sn
:t
o
.!
m
.‘
Sn
0
in
‘
‘
E
E
Sn
0
C,,
5/)
a.
.!
0
C.
I)
.-‘2
0
0
-c
-=
.
C
=
U
#{176}
0
0
N
0
0
I’-,
E
0
Sn
0’
N.
SI)
0
I
g;
<;?,o
0
-
E
E<
cS
>
,-
5
(‘4
d
.
0
C’)
z
UC
Z.
‘
M
6
KIN,
AND
KAWAI
From www.bloodjournal.org by guest on July 31, 2017. For personal use only.
HUMAN
IgA,
HALFMOLECULES
endoplasmic
277
reticula
(ER)
that
tion,
might
be producing
deletion.
This possibility
in which
whereas
somes26’27
ribosomes,
ribosomes.28
were
revealed
under
the abnormal
is supported
by
rough
that
electron-microscopic
heavy
chain
the analysis
ER of the smaller-sized
of larger-sized
cells
examina-
with
a large
amino
of membrane-bound
cells
was
was composed
composed
of
acid
poly-
of 7 and 9
7 and
I3
ACKNOWLEDGMENT
We
would
like
University
to thank
School
Professor
Tomio
advice
and
Dr.
Akira
Kawaoi
Kinji
Kakiuchi
of Medicine),
Tada
(Dept.
cooperation.
and
of Immunology,
We
are
also
Dr.
Norimichi
(Institute
Chiba
grateful
Nemoto
for Protein
University
to Kumiko
School
Sudo
(Div.
of Pathology,
Research,
Osaka
of Medicine)
for her excellent
Nihon
University),
and
for their
technical
valuable
assistance.
REFERENCES
I.
on
Despont
J-PJ,
human
terminal
IgA
deletion.
Potter
2.
entiation
cells.
3.
Kuff
of protein
i Mol
Biol
Hobbs
JR.
9:537,
Disorders
and
with
plasma
13.
a carboxy-
Exp
Proc
Hobbs
JR:
Br Med
I 3:67,
6.
Seligmann
IgG
plasma
molecular
Immunol
Heath
GK
5:199,
VC:
lgG
1969
features
cell
Blood
leukemia.
Chem
Fc
European
Immunocytoma
Society
1973,
with
of
in
a
45:305,
mice
and
a structural
Immunology,
of
cules
in
I
Clin
Invest
8.
Spiegelberg
eloma
Strassbourg,
a
HL,
patient
Heath
with
52:80A,
IgA
VC:
plasma
1973
HL,
lgG
half-mole-
cell
leukemia.
Fishkin
BG:
J Clin
Human
Invest
Biewenga
molecules
I,
in
Biological
human
Fluids
quium).
molecules.
GM,
with
Clin
I I . Kang
IgA
Res
YS,
12.
eloma
Protides
p 907
in:
Porter
JH:
lgA/2:
excretion
BS:
25th
p 899
1976
An
Biochim
of
Collo-
IgA
T,
I 73:1
half-molecules:
of Biological
abnormal
molecule
Biochem
20.
Colloquium).
A
case
Oxford,
Pergamon,
TB:
arrangeBiochem
A,
of rabbit
-y globpapain.
anti-
disulfide
bonds.
1960
in
106:41,
NatI
Defec-
mouse
myeloma
1971
E: Chain
myeloma
Proc
of
rabbit
-y A half-molecules:
Appella
mouse
of
mutants
Immunol
Separation
bivalent
89:230,
FJ:
T,
TC:
the
reduction
chain
molecules.
of the
1976
crystalline
Wissler
from
Mushinski
3.95
tempera-
Isolation
13:203,
with
by
Seki
High
IgA:
hydrolysis
Biophys
heavy
models
of 6.65
‘y A immunoglobulin
Acad
human
lgG
analysis.
23.
Acta
study,
Speigelberg
myeloma
genie
I: Human
(Proceedings
The
fragments
22.
half-
(Abstr)
Fluids
The
19, 1959
Nisonoff
Arch
Plasma
of IgA
Biophys
Sakurabayashi
RR:
Tomasi
antibodies
body
and
in
1959
Sci
USA
61:1071,
I 968
1977
Kawai
NJ,
RR:
and
21.
J Biol
in ‘y globulin.
Immunochemistry
half-
Protides
of the
24:444A,
Shim
IgA
1978,
Berman
urinary
half-molecule.
494:326,
E:
myeloma,
Pergamon
Bernier
leukemia
Loghem
(Proceedings
Oxford,
10.
Ban
Porter
chains
fragment.
proteins.J
9.
of
dodecyl
Ultracentrifugation
Fc-a
tive
by
Academic,
of human
my-
58:1259,
JB,
peptide
Calvanico
univalent
(Abstr)
half-molecules.
HK:
trypsinolysis
Biochem
I 976
25th
17.
ulin
reliability
1963
I 8.
Meetings
The
electrophoresis.
ture
abnormal-
Joint
1968
M:
York,
Fleishman
19.
Spiegelberg
61:636,
gel
Selective
1969
New
of the
88:220,
p 73 (Abstr)
7.
cell
16.
M:
chromatography.
determination
Schachman
ment
F: A half-molecule
in:
for
USA
Osborn
weight
Biochemistry.
1971
fragment,
Sci
K,
244:4406,
15.
half-mole-
immunologic
protein
the
Acad
Weber
Wilechek
by affinity
sulfate-polyacrylamide
A half-molecule
M, Mihaesco
myeloma
in
ity
NatI
14.
I
5.
P,
purification
differ-
I 975
men.
Cuatrecasas
enzyme
1974
on the
in neoplastic
A:
JL,
Clinical
patient
studies
with
1964
Jacobs
Clin
Structural
I 12:1517,
EL:
secretion
Spiegelberg
cule:
CA:
protein
I Immunol
M,
plasmacytoma.
4.
Abel
myeloma
myin:
of the
1978,
Bernier
biosynthesis
in:
Protides
the
25th
p903
24.
I 4:2 1 75,
Fanger
IgA
MW:
Biological
Spiegelberg
HL:
J Clin
(Proceedings
5, Margulies
myeloma
56:588,
DH:
and
molecule,
Pergamon,
Human
Invest
anti-
1975
half
Fluids
Oxford,
Human
and
Structure
monoclonal
Colloquium).
Weitzman
VC:
Biochemistry
GM,
of
Heath
Structural
of an
half-molecules.
25.
HL,
half-molecules.
of
1978,
IgG
1975
Mutations
in
From www.bloodjournal.org by guest on July 31, 2017. For personal use only.
278
SAKURABAVASHI.
mouse
myeloma
multiple
myeloma
globulins.
Ann
26.
analysis
myeloma
Yonezawa
cells:
and
Intern
Implications
the
Med
T,
Kitani
of membranebound
cells,
in:
for
production
85:1
10, 1976
T:
Ultrastructural
polysomes
The
human
of immuno-
16th
in human
International
Congress
of
Hematology
Kyoto,
Japan,
p 260
27.
scopic
Kitani
studies
T,
myeloma
cells.
on
KIN,
(Abstracts),
Yonezawa
T:
the
polysomes
Symp
AND
Cell
Biol
Yonezawa
T: Personal
1976,
Electronmicroin human
(Abstr)
1970
28.
KAWAI
communication
21:133,
From www.bloodjournal.org by guest on July 31, 2017. For personal use only.
1979 53: 269-278
Human IgA1 half-molecules: clinical and immunologic features in a patient
with multiple myeloma
I Sakurabayashi, K Kin and T Kawai
Updated information and services can be found at:
http://www.bloodjournal.org/content/53/2/269.full.html
Articles on similar topics can be found in the following Blood collections
Information about reproducing this article in parts or in its entirety may be found online at:
http://www.bloodjournal.org/site/misc/rights.xhtml#repub_requests
Information about ordering reprints may be found online at:
http://www.bloodjournal.org/site/misc/rights.xhtml#reprints
Information about subscriptions and ASH membership may be found online at:
http://www.bloodjournal.org/site/subscriptions/index.xhtml
Blood (print ISSN 0006-4971, online ISSN 1528-0020), is published weekly by the American Society of
Hematology, 2021 L St, NW, Suite 900, Washington DC 20036.
Copyright 2011 by The American Society of Hematology; all rights reserved.