Mimicry of pre-B cell receptor signaling by activation of the tyrosine kinase Blk.
During B lymphoid ontogeny, assembly of the pre-B cell receptor (BCR) is a principal developmental checkpoint at which several Src-related kinases may play redundant roles. Here the Src-related kinase Blk is shown to effect functions associated with the pre-BCR. B lymphoid expression of an active Blk mutant caused proliferation of B progenitor cells and enhanced responsiveness of these cells to interleukin 7. In mice lacking a functional pre-BCR, active Blk supported maturation beyond the pro-B cell stage, suppressed VH to DJH rearrangement, relieved selection for productive heavy chain rearrangement, and stimulated kappa rearrangement. These alterations were accompanied by tyrosine phosphorylation of immunoglobulin beta and Syk, as well as changes in gene expression consistent with developmental maturation. Thus, sustained activation of Blk induces responses normally associated with the pre-BCR.
Tretter
Theresa
T
Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Ross
Ashley E
AE
Dordai
Dominic I
DI
Desiderio
Stephen
S
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D002478:Cells, Cultured; D004789:Enzyme Activation; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D015851:Interleukin-7 / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism*
D007143:Immunoglobulin Heavy Chains; D007145:Immunoglobulin kappa-Chains; D015851:Interleukin-7; D008562:Membrane Glycoproteins; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell; D019061:src-Family Kinases