Immunoglobulin-mediated signal transduction in B cells from CD45-deficient mice.
CD45 expression is essential for immunoglobulin (Ig)-mediated B cell activation. Treatments with either anti-Ig or anti-CD45 suggest that CD45 may facilitate early signaling events such as calcium mobilization, and phosphoinositide hydrolyis as well as later events leading to transcription of genes such as c-myc. To examine the role of CD45 more extensively, CD45-deficient mice were generated by disruption of exon 6. Although normal numbers of B cells were found in peripheral lymphoid tissues, CD45-deficient cells failed to proliferate upon IgM crosslinking. In the present study, we demonstrate that the fraction of high buoyant density B cells is reduced while low buoyant density cells are increased. Moreover, there is a significant decline in the number of splenic B cells of the mature IgDhi, IgMlo phenotype. Although both the basal and anti-Ig-induced levels of phosphorylation of Ig-alpha and phospholipase C gamma 2 are indistinguishable from that observed in CD45+ control B cells, a major distinction was found in Ca2+ mobilization. While anti-Ig-induced mobilization of intracellular Ca2+ stores was normal, influx from extracellular sources was abrogated. This finding reveals a novel pathway of regulating B cell responses mediated by CD45.
Benatar
T
T
Wellesley Hospital Research Institute, University of Toronto, Canada.
Carsetti
R
R
Furlonger
C
C
Kamalia
N
N
Mak
T
T
Paige
C J
CJ
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D015153:Blotting, Western; D051925:CD79 Antigens; D002118:Calcium / Q000378:metabolism; D004789:Enzyme Activation; D005434:Flow Cytometry; D007075:Immunoglobulin M / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010641:Phenotype; D051966:Phospholipase C gamma; D010766:Phosphorylation; D011233:Precipitin Tests; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism
D015703:Antigens, CD; D051925:CD79 Antigens; C497882:Cd79a protein, mouse; D007075:Immunoglobulin M; D007527:Isoenzymes; D011947:Receptors, Antigen, B-Cell; D017493:Leukocyte Common Antigens; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D002118:Calcium