Cutting edge: A/WySnJ transitional B cells overexpress the chromosome 15 proapoptotic Blk gene and succumb to premature apoptosis.
Better knowledge of peripheral B lymphocyte homeostasis is needed to address the human hypogammaglobulinemia diseases. A defect in the Bcmd gene shortens the B cell life span and causes B cell deficiency in A/WySnJ mice. Previous genetic mapping placed Bcmd near Srebf2 on chromosome 15. Inspection of the human chromosome 22 syntenic region identified the proapoptotic Bik gene as a candidate. Two mapping methods placed the homologous mouse gene, Blk, near Srebf2. The Blk genomic structure was highly homologous to BIK: Sequence analysis ruled out coding region mutations, but Blk transcripts were overly abundant in sorted A/WySnJ T1 B cells. Moreover, enriched transitional B cells showed a cell-autonomous defect leading to excessive apoptosis. Thus, Bcmd may be a direct mutation in Blk, or in a gene involved in Blk regulation, such that excess expression pushes the A/WySnJ transitional B cells past the apoptosis checkpoint to cell death.
Amanna
I J
IJ
Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin, Madison, WI 53706, USA.
Clise-Dwyer
K
K
Nashold
F E
FE
Hoag
K A
KA
Hayes
C E
CE
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000276:immunology; D051017:Apoptosis Regulatory Proteins; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D051379:Mice; D008805:Mice, Inbred A; D024101:Mitochondrial Proteins; D011110:Polymorphism, Genetic / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D021101:Radiation Hybrid Mapping; D011995:Recombination, Genetic / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C111741:Bik protein, mouse; D002352:Carrier Proteins; D024101:Mitochondrial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2