AID and caspase 8 shape the germinal center response through apoptosis

Bryant Boulianne, Olga L. Rojas, Dania Haddad, Ahmad Zaheen, Anat Kapelnikov, Thanh Nguyen, Conglei Li, Razq Hakem, Jennifer L. Gommerman, Alberto Martin

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)5840-5847
Number of pages8
JournalJournal of Immunology
Volume191
Issue number12
DOIs
Publication statusPublished - 15 Dec 2013

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    Boulianne, B., Rojas, O. L., Haddad, D., Zaheen, A., Kapelnikov, A., Nguyen, T., Li, C., Hakem, R., Gommerman, J. L., & Martin, A. (2013). AID and caspase 8 shape the germinal center response through apoptosis. Journal of Immunology, 191(12), 5840-5847. https://doi.org/10.4049/jimmunol.1301776