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

Nat Immunol. 2012 May 6;13(6):604-11. 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 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocytes / classification
  • B-Lymphocytes / immunology*
  • Flow Cytometry
  • Immunoglobulin A / immunology
  • Immunoglobulin Class Switching / immunology*
  • Immunoglobulin G / immunology
  • Immunologic Memory / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • Receptor Tyrosine Kinase-like Orphan Receptors / genetics
  • Receptor Tyrosine Kinase-like Orphan Receptors / immunology*
  • Receptors, Antigen, B-Cell / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT1 Transcription Factor / immunology
  • Specific Pathogen-Free Organisms
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / immunology*
  • Transcription, Genetic / immunology


  • Immunoglobulin A
  • Immunoglobulin G
  • RNA, Messenger
  • Receptors, Antigen, B-Cell
  • STAT1 Transcription Factor
  • Stat1 protein, mouse
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Receptor Tyrosine Kinase-like Orphan Receptors