Unexpected role for the B cell-specific Src family kinase B lymphoid kinase in the development of IL-17-producing γδ T cells

J Immunol. 2010 Dec 1;185(11):6518-27. doi: 10.4049/jimmunol.1002766. Epub 2010 Oct 25.

Abstract

The Ag receptors on αβ and γδ T cells differ not only in the nature of the ligands that they recognize but also in their signaling potential. We hypothesized that the differences in αβ- and γδTCR signal transduction were due to differences in the intracellular signaling pathways coupled to these two TCRs. To investigate this, we used transcriptional profiling to identify genes encoding signaling molecules that are differentially expressed in mature αβ and γδ T cell populations. Unexpectedly, we found that B lymphoid kinase (Blk), a Src family kinase expressed primarily in B cells, is expressed in γδ T cells but not in αβ T cells. Analysis of Blk-deficient mice revealed that Blk is required for the development of IL-17-producing γδ T cells. Furthermore, Blk is expressed in lymphoid precursors and, in this capacity, plays a role in regulating thymus cellularity during ontogeny.

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocyte Subsets / enzymology*
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism
  • Cell Differentiation / immunology*
  • Epitopes, B-Lymphocyte / immunology
  • Gene Knock-In Techniques
  • Interleukin-17 / biosynthesis*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell, gamma-delta / biosynthesis*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Thymus Gland / embryology
  • Thymus Gland / enzymology
  • Thymus Gland / immunology
  • src-Family Kinases / biosynthesis
  • src-Family Kinases / deficiency
  • src-Family Kinases / physiology*

Substances

  • Epitopes, B-Lymphocyte
  • Il17a protein, mouse
  • Interleukin-17
  • Receptors, Antigen, T-Cell, gamma-delta
  • protein-tyrosine kinase p55(blk)
  • src-Family Kinases