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Nat Immunol. 2012 May 6;13(6):604-11. doi: 10.1038/ni.2294.

Divergent transcriptional programming of class-specific B cell memory by T-bet and RORα.

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1
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA.

Abstract

Antibody class defines function in B cell immunity, but how class is propagated into B cell memory remains poorly understood. Here we demonstrate that memory B cell subsets unexpectedly diverged across antibody class through differences in the effects of major transcriptional regulators. Conditional genetic deletion of the gene encoding the transcription factor T-bet selectively blocked the formation and antigen-specific response of memory B cells expressing immunoglobulin G2a (IgG2a) in vivo. Cell-intrinsic expression of T-bet regulated expression of the transcription factor STAT1, steady-state cell survival and transcription of IgG2a-containing B cell antigen receptors (BCRs). In contrast, the transcription factor RORα and not T-bet was expressed in IgA(+) memory B cells, with evidence that knockdown of RORα mRNA expression and chemical inhibition of transcriptional activity also resulted in lower survival and BCR expression of IgA(+) memory B cells. Thus, divergent transcriptional regulators dynamically maintain subset integrity to promote specialized immune function in class-specific memory B cells.

PMID:
22561605
PMCID:
PMC3362691
DOI:
10.1038/ni.2294
[Indexed for MEDLINE]
Free PMC Article

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