The TACI receptor regulates T-cell-independent marginal zone B cell responses through innate activation-induced cell death

William Arthur Figgett, Kirsten Fairfax, Fabien Vincent, Melanie Le Page, Indzi Katik, Devy Deliyanti, Pin Shie Quah, Pali Verma, Raelene Joy Grumont, Steven Demetrious Gerondakis, Paul John Hertzog, Lorraine A O'Reilly, Andreas Strasser, Fabienne Mackay-Fisson

Research output: Contribution to journalArticleResearchpeer-review

38 Citations (Scopus)

Abstract

Activation-induced cell death (AICD) plays a critical role in immune homeostasis and tolerance. In T-cell-dependent humoral responses, AICD of B cells is initiated by Fas ligand (FasL) on T cells, stimulating the Fas receptor on B cells. In contrast, T-cell-independent B cell responses involve innate-type B lymphocytes, such as marginal zone (MZ) B cells, and little is known about the mechanisms that control AICD during innate B cell responses to Toll-like receptor (TLR) activation. Here, we show that MZ B cells undergo AICD in response to TLR4 activation in vivo. The transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI) receptor and TLR4 cooperate to upregulate expression of both FasL and Fas on MZ B cells and also to repress inhibitors of Fas-induced apoptosis signaling. These findings demonstrate an unappreciated role for TACI and its ligands in the regulation of AICD during T-cell-independent B cell responses.
Original languageEnglish
Pages (from-to)573 - 583
Number of pages11
JournalImmunity
Volume39
Issue number3
DOIs
Publication statusPublished - 2013

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