Abnormal peripheral lymphocyte function in c-abl mutant mice

Cell Immunol. 1996 Aug 25;172(1):100-7. doi: 10.1006/cimm.1996.0220.

Abstract

The proto-oncogene c-abl encodes a tyrosine kinase that is hypothesized to function in proliferation-stimulatory signaling pathways. Previous work on mice homozygous for targeted mutations in the c-abl gene (ablml and abl2 mutant strains) has demonstrated multiple defects, including a susceptibility to infections that results in a high mortality rate after weaning. FACS analysis of the hemopoietic system of c-abl mutants demonstrated variable reductions in B and T lymphocytes in adult bone marrow, thymus, spleen, and peripheral blood. In addition, bone marrow from mutants showed a decreased ability to respond to interleukin-7. We further found that B cells from ablm1 mice had a reduced ability to respond to lipopolysaccharide (decreased to 10% of control response) that was dependent on the culture conditions and the tissue of origin of B cells. Peripheral blood from the mutants also had a reduced response to the T cell mitogen concanavalin A. Immune response in ablm1 mice as determined by the mixed lymphocyte response and the sheep red blood cell plaque-forming assay was grossly normal. These findings suggest that although specific signaling pathways in lymphocytes may involve c-Abl, the immune system can function in the absence of a normal c-abl gene product.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • Cell Division
  • Cells, Cultured
  • Homozygote
  • Humans
  • Lipopolysaccharides / pharmacology
  • Lymphoid Tissue / drug effects
  • Lymphoid Tissue / immunology
  • Mice
  • Mice, Mutant Strains
  • Mitogens / pharmacology
  • Proto-Oncogene Proteins c-abl / genetics
  • Proto-Oncogene Proteins c-abl / immunology*
  • Sheep
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*

Substances

  • Lipopolysaccharides
  • Mitogens
  • Proto-Oncogene Proteins c-abl