title: Blk haploinsufficiency impairs the development, but enhances the functional responses, of MZ B cells.
abstract: 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.
authors: Department of Microbiology and Immunology, State University of New York Upstate Medical University, Syracuse, NY 13210, USA.
authors: Elizabeth M
authors: EM
authors: Samuelson
authors: Renee M
authors: RM
authors: Laird
authors: Alexander C
authors: AC
authors: Maue
authors: Rosemary
authors: R
authors: Rochford
authors: Sandra M
authors: SM
authors: Hayes
mesh_terms: D000818:Animals; D000955:Antigens, T-Independent / Q000276:immunology; D015551:Autoimmunity; D016175:B-Lymphocyte Subsets / Q000201:enzymology* / Q000276:immunology*; D002454:Cell Differentiation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D057895:Haploinsufficiency; D020381:Interleukin-17 / Q000276:immunology; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D015398:Signal Transduction; D019061:src-Family Kinases / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000955:Antigens, T-Independent; D020381:Interleukin-17; D011947:Receptors, Antigen, B-Cell; C082599:protein-tyrosine kinase p55(blk); D019061:src-Family Kinases; D048049:Extracellular Signal-Regulated MAP Kinases