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 (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.
Hardin
J D
JD
Department of Biochemistry, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
Boast
S
S
Schwartzberg
P L
PL
Lee
G
G
Alt
F W
FW
Stall
A M
AM
Goff
S P
SP
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002455:Cell Division; D002478:Cells, Cultured; D006720:Homozygote; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008221:Lymphoid Tissue / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D008934:Mitogens / Q000494:pharmacology; D000090063:Proto-Oncogene Mas; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000276:immunology*; D012756:Sheep; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
D008070:Lipopolysaccharides; C000715470:MAS1 protein, human; D008934:Mitogens; D000090063:Proto-Oncogene Mas; D016315:Proto-Oncogene Proteins c-abl