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Blk haploinsufficiency impairs the development, but enhances the functional responses, of MZ B cells
Author(s) -
Samuelson Elizabeth M,
Laird Renee M,
Maue Alexander C,
Rochford Rosemary,
Hayes Sandra M
Publication year - 2012
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2011.76
Subject(s) - b cell , microbiology and biotechnology , biology , haploinsufficiency , immunology , antibody , phenotype , biochemistry , gene
Blk was identified two decades ago as a B‐cell‐specific member of the Src family of tyrosine kinases. Recent studies, however, have discovered that Blk is expressed in many cell types outside of the B lineage, including early thymic precursors, interleukin‐17‐producing γδ T cells and pancreatic β‐cells. In light of these recent discoveries, we performed a more comprehensive analysis of Blk expression patterns in hematopoietic cells and found that Blk is differentially expressed in mature B‐cell subsets, with marginal zone (MZ) B cells expressing high levels, B1 B cells expressing intermediate‐to‐high levels and follicular (FO) B cells expressing low levels of Blk. To determine whether these differences in Blk expression levels reflected differential requirements for Blk in MZ, B1 and FO B‐cell development, we analyzed the effects of reducing and eliminating Blk expression on B‐cell development. We report that both Blk haploinsufficiency and Blk deficiency impaired the generation of MZ B cells. Moreover, although there were fewer MZ B cells in Blk +/− and Blk −/− mice as compared with Blk +/+ mice, Blk‐mutant MZ B cells were hyper‐responsive to B‐cell receptor stimulation, both in vitro and in vivo . Thus, this study has revealed a previously unappreciated role for Blk in the development and activation of MZ B cells.