Divergent transcriptional programming of class-specific B cell memory by T-bet and ROR alpha

作者：Wang Nathaniel S; McHeyzer Williams Louise J; Okitsu Shinji L; Burris Thomas P; Reiner Steven L; McHeyzer Williams Michael G^*

来源：Nature Immunology, 2012, 13(6): 604-+.

DOI：10.1038/ni.2294

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 ROR alpha and not T-bet was expressed in IgA(+) memory B cells, with evidence that knockdown of ROR alpha 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.

• 出版日期2012-6