Negative regulation of apoptotic death in immature B cells by CD45.
Cross-linking of membrane IgM receptor on B cells induces tyrosine phosphorylation within 1 min. This biochemical alteration triggers a cascade of signaling events which ultimately leads to activation in mature B cells but growth arrest and cell death by apoptosis in immature B cells. To study the mechanisms underlying the bifurcation of signals, we chose to examine the role of receptor-type protein tyrosine phosphatase (PTP) CD45 using CD45- clones isolated from an immature B cell line WEHI-231. Here we report that in CD45- clones, tyrosine phosphorylation was constitutively induced but not enhanced by anti-IgM stimulation and anti-IgM-induced Ca2+ flux was slightly delayed but evidently prolonged. Further, the degree of growth arrest and DNA fragmentation induced by anti-IgM antibody was more evident in CD45- clones than the parental cells. These results indicate that initial alterations in signaling are effectively transduced into effector signals and that IgM receptor-mediated growth arrest and apoptosis in immature B cells are negatively regulated by CD45.
Ogimoto
M
M
Tokyo Metropolitan Institute for Neuroscience, Japan.
Katagiri
T
T
Mashima
K
K
Hasegawa
K
K
Mizuno
K
K
Yakura
H
H
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D016175:B-Lymphocyte Subsets / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D002460:Cell Line; D005434:Flow Cytometry; D007075:Immunoglobulin M / Q000502:physiology; D017493:Leukocyte Common Antigens / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D010766:Phosphorylation; D015290:Second Messenger Systems / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism
D007075:Immunoglobulin M; D014443:Tyrosine; D017493:Leukocyte Common Antigens; D002118:Calcium