Btk regulates multiple stages in the development and survival of B-1 cells

Cristina M. Contreras, Kristina E. Halcomb, Lindsey Randle, Rochelle M. Hinman, Toni Gutierrez, Stephen H. Clarke, Anne B. Satterthwaite

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

B-1 cells are important players in the first line of defense against pathogens. According to current models for the origin of B-1 cells, they either represent a separate lineage from conventional B-2 cells or differentiate from conventional B-2 cells via an intermediate, B-1int, in response to positive selection by antigen. Here we show that Btk, a Tec family kinase that mediates B cell antigen receptor (BCR) signaling, is required at multiple stages of B-1 cell development. VH12 anti-phosphatidylcholine (PtC) IgH transgenic mice provide a model for the induced differentiation of B-1 cells. This transgene selects for PtC-reactive cells and induces them to adopt a B-1 phenotype. Both processes have been shown to depend on Btk. To determine whether this is secondary to a requirement for Btk in the development of mature B-2 cells, we crossed VH12 transgenic mice to mice expressing low levels of Btk. B-2 cell development occurs normally in Btklo mice despite reduced responsiveness to BCR crosslinking. Analysis of VH12.Btklo mice reveals that Btk regulates the B-1int to B-1 transition and/or the survival of splenic B-1 cells, in part via a mechanism independent of its role in BCR signaling. We also show that Btk mediates the survival of, and expression of IL-10 by, those B-1 cells that do develop and migrate to the peritoneum. Multiple roles for Btk in B-1 cell development and maintenance may explain the particular sensitivity of this population to mutations in components of Btk signaling pathways.

Original languageEnglish (US)
Pages (from-to)2719-2728
Number of pages10
JournalMolecular Immunology
Volume44
Issue number10
DOIs
StatePublished - Apr 1 2007

Keywords

  • B cell development
  • BCR signaling
  • IL-10
  • Lyn
  • Phosphatidylcholine

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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    Contreras, C. M., Halcomb, K. E., Randle, L., Hinman, R. M., Gutierrez, T., Clarke, S. H., & Satterthwaite, A. B. (2007). Btk regulates multiple stages in the development and survival of B-1 cells. Molecular Immunology, 44(10), 2719-2728. https://doi.org/10.1016/j.molimm.2006.11.023