B Cell Development in Bone Marrow and Peripheral
Lymphoid Tissue Part II
March 23, 2009
10:00-11:00
THE FOUR PHASES OF B CELL DEVELOPMENT
CHANGES IN IMMUNOGLOBULIN EXPRESSION DURING
B CELL DEVELOPMENT IN THE BONE MARROW
ANTIGEN DEPENDENT
Random generation of repertoire results in self-reactive B cells
ELIMINATION OF SELF REACTIVE B CELLS
Anergy is the inability to respond
STRONG INTERACTION WITH SELF CAN TRIGGER RECEPTOR
EDITING AND RESCUE THE B CELL
TICKLE ME OR I DIE
B cells move between blood, lymphoid tissue,and lymphatics
The largest collection of lymphoid tissue is in the gut
The keys to survival: Entry into a follicle
Stimulation with antigen
B CELLS GET SURVIVAL SIGNALS IN PRIMARY FOLLICLES
Recirculating B cells try to gain access to primary follicles
Primary follicles are organized structures with FDCs
ANTIGEN STIMULATED B CELLS FORM GERMINAL CENTERS
B cells that find antigen form a primary focus in the T cell zone
Cells from the primary focus enter follicle and form a germinal center
ISOTYPE SWITCHING OCCURS IN GERMINAL CENTERS
S regions are repetitive sequence 5’ to every C except Cd
Recombination occurs between S regions
Intervening DNA is deleted and VDJ becomes associated with a new CH
AFFFINITY MATURATION OCCURS IN GERMINAL CENTERS
The process that increases diversity is called SOMATIC HYPERMUTATION
The result is AFFINITY MATURATION
B CELLS DIFFERENTIATE INTO MEMORY OR PLASMA CELLS
IN SECONDARY LYMPHOID TISSUE
B cells must enter germinal center to become memory cells
B cells can become plasma cells without entering the germinal center
A SECOND POPULATION OF B CELLS THAT COMES FIRST
B cells are first produced in the bone marrow after birth
B-1 B cells arise during embryonic development
B-1 cells were first identified by expression of CD5
B-1 cells are less abundant, but predominate in pleural and
peritoneal cavities
CLL is frequently a CD5 expressing tumor
CD5 VS CONVENTIONAL B CELLS
USE OF MICROARRAY ANALYSIS TO DEFINE B CELL STAGES
EXPRESSION PROFILING OF LYMPHOMAS
Nature (2000)
403:503
FOLLICULAR LYMPHOMAS RETAIN CHARACTERISTICS OF
GERMINAL CENTER B CELLS
TUMOR COUNTERPARTS OF NORMAL CELLS
B CELL LIFE CYCLE
SUMMARY: B CELL DEVELOPMENT IN BONE MARROW
Phase 1
Phase 2
ANTIGEN DEPENDENT
SUMMARY: B CELL DEVELOPMENT IN SECONDARY LYMPHOID TISSUE
Phase 3
IgD
Phase 4