B cell receptor signal strength determines B cell fate

Nat Immunol. 2004 Mar;5(3):317-27. doi: 10.1038/ni1036. Epub 2004 Feb 1.


B cell receptor (BCR)-mediated antigen recognition is thought to regulate B cell differentiation. BCR signal strength may also influence B cell fate decisions. Here, we used the Epstein-Barr virus protein LMP2A as a constitutively active BCR surrogate to study the contribution of BCR signal strength in B cell differentiation. Mice carrying a targeted replacement of Igh by LMP2A leading to high or low expression of the LMP2A protein developed B-1 or follicular and marginal zone B cells, respectively. These data indicate that BCR signal strength, rather than antigen specificity, determines mature B cell fate. Furthermore, spontaneous germinal centers developed in gut-associated lymphoid tissue of LMP2A mice, indicating that microbial antigens can promote germinal centers independently of BCR-mediated antigen recognition.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Cell Differentiation
  • Cells, Cultured
  • Digestive System / immunology
  • Female
  • Gene Targeting
  • Germinal Center / cytology
  • Germinal Center / immunology*
  • Male
  • Mice
  • Mice, Transgenic
  • Peyer's Patches / anatomy & histology
  • Peyer's Patches / immunology
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, B-Cell / metabolism*
  • Signal Transduction*
  • Stem Cells / physiology
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / metabolism


  • EBV-associated membrane antigen, Epstein-Barr virus
  • Receptors, Antigen, B-Cell
  • Viral Matrix Proteins