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

J Immunol. 2001 Dec 1;167(11):6069-72. doi: 10.4049/jimmunol.167.11.6069.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Apoptosis / genetics*
  • Apoptosis / immunology
  • Apoptosis Regulatory Proteins
  • B-Lymphocyte Subsets / cytology*
  • B-Lymphocyte Subsets / metabolism*
  • B-Lymphocyte Subsets / pathology
  • Carrier Proteins / biosynthesis*
  • Carrier Proteins / genetics*
  • Cells, Cultured
  • Gene Expression Regulation* / immunology
  • Humans
  • Mice
  • Mice, Inbred A
  • Mitochondrial Proteins*
  • Polymorphism, Genetic / immunology
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Radiation Hybrid Mapping
  • Recombination, Genetic / immunology

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • Bik protein, mouse
  • Carrier Proteins
  • Mitochondrial Proteins
  • Proto-Oncogene Proteins c-bcl-2