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

Academic Article
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Overview

related to degree

  • Wang, Nathaniel, Ph.D. in Biology, Scripps Research 2008 - 2012

authors

  • Wang, Nathaniel
  • McHeyzer-Williams, L. J.
  • Okitsu, S. L.
  • Burris, Thomas
  • Reiner, S. L.
  • McHeyzer-Williams, Michael G.

publication date

  • 2012

journal

  • Nature Immunology  Journal

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.

subject areas

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

PubMed Central ID

  • PMC3362691

International Standard Serial Number (ISSN)

  • 1529-2908

Digital Object Identifier (DOI)

  • 10.1038/ni.2294

PubMed ID

  • 22561605
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Additional Document Info

start page

  • 604

end page

  • 11

volume

  • 13

issue

  • 6

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