AID and caspase 8 shape the germinal center response through apoptosis.
Germinal centers (GCs) are clusters of activated B cells that form in secondary lymphoid organs during a T-dependent immune response. B cells enter GCs and become rapidly proliferating centroblasts that express the enzyme activation-induced deaminase (AID) to undergo somatic hypermutation and class-switch recombination. Centroblasts then mature into centrocytes to undergo clonal selection. Within the GC, the highest affinity B cell clones are selected to mature into memory or plasma cells while lower affinity clones undergo apoptosis. We reported previously that murine Aicda(-/-) GC B cells have enhanced viability and accumulate in GCs. We now show that murine Aicda(-/-) GC B cells accumulate as centrocytes and inefficiently generate plasma cells. The reduced rate of plasma cell formation was not due to an absence of AID-induced DNA lesions. In addition, we show that the deletion of caspase 8 specifically in murine GC-B cells results in larger GCs and a delay in affinity maturation, demonstrating the importance of apoptosis in GC homeostasis and clonal selection.
Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Bryant
B
Boulianne
Olga L
OL
Rojas
Dania
D
Haddad
Ahmad
A
Zaheen
Anat
A
Kapelnikov
Thanh
T
Nguyen
Conglei
C
Li
Razq
R
Hakem
Jennifer L
JL
Gommerman
Alberto
A
Martin
D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000276:immunology; D017209:Apoptosis / Q000502:physiology*; D056735:Autoimmune Lymphoproliferative Syndrome / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D053181:Caspase 8 / Q000235:genetics / Q000502:physiology*; D002455:Cell Division; D060966:Clonal Selection, Antigen-Mediated; D003564:Cytidine Deaminase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D053903:DNA Breaks, Double-Stranded; D018858:Germinal Center / Q000276:immunology* / Q000473:pathology; D007114:Immunization; D017578:Immunoglobulin Class Switching; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010950:Plasma Cells / Q000473:pathology; D011828:Radiation Chimera; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D027041:Somatic Hypermutation, Immunoglobulin; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D000941:Antigens; D011947:Receptors, Antigen, B-Cell; C505526:Casp8 protein, mouse; D053181:Caspase 8; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase