Abnormal peripheral lymphocyte function in c-abl mutant mice

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 (abl(m1) and abl(2) mutant strains) has demonstrated multiple defects, including a susceptibility to infections that results in a high mortality rate after weaning. FAGS 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 abl(ml) 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 abl(m1) 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. (C) 1996 Academic Press, Inc.