AID and Caspase 8 Shape the Germinal Center Response through Apoptosis

被引：14

作者：

Boulianne, Bryant ^{[1
]}

Rojas, Olga L. ^{[1
]}

Haddad, Dania ^{[1
]}

Zaheen, Ahmad ^{[1
]}

Kapelnikov, Anat ^{[1
]}

Thanh Nguyen ^{[1
]}

Li, Conglei ^{[1
]}

Hakem, Razq ^{[1
]}

Gommerman, Jennifer L. ^{[1
]}

Martin, Alberto ^{[1
]}

机构：

[1] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada

来源：

JOURNAL OF IMMUNOLOGY | 2013年 / 191卷 / 12期

基金：

加拿大健康研究院;

关键词：

INDUCED CYTIDINE DEAMINASE; PRIMARY IMMUNE-RESPONSE; CENTER B-CELLS; IN-SITU; ACTIVATION; EXPRESSION; FAS; SELECTION; AFFINITY; MEMORY;

D O I：

10.4049/jimmunol.1301776

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

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.

引用

页码：5840 / 5847

页数：8

共 42 条

[1]

Germinal center dark and light zone organization is mediated by CXCR4 and CXCR5 [J].