TY - JOUR
T1 - AID and caspase 8 shape the germinal center response through apoptosis
AU - Boulianne, Bryant
AU - Rojas, Olga L.
AU - Haddad, Dania
AU - Zaheen, Ahmad
AU - Kapelnikov, Anat
AU - Nguyen, Thanh
AU - Li, Conglei
AU - Hakem, Razq
AU - Gommerman, Jennifer L.
AU - Martin, Alberto
PY - 2013/12/15
Y1 - 2013/12/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84890381835&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1301776
DO - 10.4049/jimmunol.1301776
M3 - Article
AN - SCOPUS:84890381835
VL - 191
SP - 5840
EP - 5847
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 12
ER -