Cutting edge: A/WySnJ transitional B cells overexpress the chromosome 15 proapoptotic Blk gene and succumb to premature apoptosis

IJ Amanna, K Clise-Dwyer, FE Nashold… - The Journal of …, 2001 - journals.aai.org
IJ Amanna, K Clise-Dwyer, FE Nashold, KA Hoag, CE Hayes
The Journal of Immunology, 2001journals.aai.org
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 …
Abstract
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.
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