B-cell receptor cross-linking delays activation-induced cytidine deaminase induction and inhibits class-switch recombination to IgE

J Allergy Clin Immunol. 2008 Jan;121(1):191-196.e2. doi: 10.1016/j.jaci.2007.08.008. Epub 2007 Sep 27.


Background: During differentiation, B cells receive signals by antigen through the B-cell receptor (BCR) and signals that induce isotype switching.

Objective: We sought to investigate the effects of BCR ligation on isotype switching.

Methods: Naive B cells from BALB/c mice were stimulated with LPS plus IL-4 alone or plus anti-IgM (0.1-10 mug/mL). IgE and IgG1 levels in supernatants were measured by means of ELISA on day 6. Cmu or Cvarepsilon germline transcripts, activation-induced cytidine deaminase (AID), and Imu-Cvarepsilon postswitch transcripts were measured by means of RT-PCR. Deletional switch recombination was assessed by means of digestion circularization PCR of Smu-Svarepsilon products.

Results: BCR cross-linking inhibited IgE and IgG1 switching in a dose-dependent fashion. This was not due to inhibition of proliferation, increased apoptosis, or cell death. BCR cross-linking had no effect on Cmu or Cvarepsilon germline transcripts but suppressed the generation of Smu-Svarepsilon switch products and Imu-Cvarepsilon postswitch transcripts and caused a delay in the expression of AID mRNA, with decreased expression on days 2 and 3 after stimulation. Concomitantly, the number of DNA repair foci at the IgH locus on day 3 was significantly decreased. AID expression and activity became normal on day 4, but isotype switching remained profoundly diminished 8 days after stimulation.

Conclusion: BCR cross-linking delays AID expression. This might interfere with class-switch recombination by disrupting the temporal coordination of signals that lead to class-switch recombination.

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocytes / metabolism
  • Cells, Cultured
  • Cytidine Deaminase / biosynthesis*
  • Enzyme Induction
  • Immunoglobulin Class Switching / genetics*
  • Immunoglobulin Class Switching / immunology*
  • Immunoglobulin E / biosynthesis*
  • Immunoglobulin G / biosynthesis
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Antigen, B-Cell / metabolism*
  • Recombination, Genetic*


  • Immunoglobulin G
  • Receptors, Antigen, B-Cell
  • Immunoglobulin E
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase