CD45 is required for CD40-induced inhibition of DNA synthesis and regulation of c-Jun NH2-terminal kinase and p38 in BAL-17 B cells.
Stimulation of B cell antigen receptor (BCR) may induce proliferation, differentiation, or apoptosis, depending upon the maturational stage of the cell and the presence or absence of signals transmitted via coreceptors. One such signal is delivered via CD40; for instance, ligation of CD40 rescues B cells from BCR-induced apoptosis. Here we show that, in contrast to WEHI-231 cells, CD40 ligation did not reverse BCR-induced growth inhibition in the BAL-17 mature B cell line and CD40 ligation itself inhibited proliferation. This inhibitory signaling was not observed in CD45-deficient cells. Further analyses demonstrate that transfection of dominant-negative form of SEK1 or treatment with SB203580 strongly reduced CD40-induced inhibition of BAL-17 proliferation, suggesting a requirement for c-Jun NH2-terminal kinase and p38 in CD40-induced inhibition of proliferation. Interestingly, CD40-initiated activation of c-Jun NH2-terminal kinase and p38 was enhanced and sustained in CD45-deficient cells, and these phenotypes were reversed by transfecting CD45 gene. However, CD40-mediated induction of cell surface molecules was not affected in CD45-deficient cells. Taken collectively, these results suggest that CD45 exerts a decisive effect on selective sets of CD40-mediated signaling pathways, dictating B cell fate.
Arimura
Y
Y
Department of Immunology and Signal Transduction, Tokyo Metropolitan Institute for Neuroscience, Tokyo Metropolitan Organization for Medical Research, Fuchu, Tokyo 183-8526, Japan.
Ogimoto
M
M
Mitomo
K
K
Katagiri
T
T
Yamamoto
K
K
Volarevic
S
S
Mizuno
K
K
Yakura
H
H
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology*; D019013:CD40 Antigens / Q000502:physiology*; D002455:Cell Division; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis*; D004789:Enzyme Activation; D048031:JNK Mitogen-Activated Protein Kinases; D017493:Leukocyte Common Antigens / Q000502:physiology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D051381:Rats; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases
D019013:CD40 Antigens; D011947:Receptors, Antigen, B-Cell; D004247:DNA; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D017493:Leukocyte Common Antigens