Defective CD19-dependent signaling in B-1a and B-1b B lymphocyte subpopulations

Goutam Sen, Hsin Jung Wu, Gabriel Bikah, Chandrasekar Venkataraman, Darrell A. Robertson, E. Charles Snow, Subbarao Bondada

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Peritoneal and pleural cavities in mice and humans contain a unique population of B-lymphocytes called B-1 cells that are defective in B cell antigen receptor (BCR) signaling but have an increased propensity to produce autoantibodies. Several molecules such as Btk, Vav, and CD19 known to be important for BCR signaling have been shown to be critical for the development of B-1 cells from undefined precursors. Here we demonstrate that B-1 cell unresponsiveness to BCR cross-linking is in part due to defective signaling through CD19, a molecule known to modulate signaling thresholds in B cells. The defective CD19 signaling is manifested in reduced synergy between mIgM and CD19 to stimulate calcium mobilization in B-1 cells. BCR induced tyrosine phosphorylation of CD19 was transient in B-1 cells while it was prolonged in splenic B-2 cells. In both B-1 and B-2 cells BCR cross-linking induced a modest increase of CD19 associated Lyn, a Src family protein tyrosine kinase (PTK) thought to be important for CD19 phosphorylation. However, the tyrosine phosphorylated CD19 in B-1 cells binds less phosphatidylinositol 3-kinase (PI3-K) compared to B-2 cells. Most interestingly, we find that Vav-1 and Vav-2, proteins thought to be critical for CD19 signal transduction, are severely reduced in B-1 cells resulting in a complete absence of any CD19 associated Vav. Also we showed that both B-1a and B-1b B cells failed to proliferate in response to BCR cross-linking which in part appears to be due to defects in CD19 mediated amplification of BCR induced calcium mobilization.

Original languageEnglish (US)
Pages (from-to)57-68
Number of pages12
JournalMolecular Immunology
Volume39
Issue number1-2
DOIs
StatePublished - Sep 15 2002
Externally publishedYes

Keywords

  • Autoimmunity
  • B-1 cells
  • BCR
  • CD19
  • Vav

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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    Sen, G., Wu, H. J., Bikah, G., Venkataraman, C., Robertson, D. A., Snow, E. C., & Bondada, S. (2002). Defective CD19-dependent signaling in B-1a and B-1b B lymphocyte subpopulations. Molecular Immunology, 39(1-2), 57-68. https://doi.org/10.1016/S0161-5890(02)00047-0