Immunoglobulin-mediated signal transduction in B cells from CD45-deficient mice

• Published in: The Journal of experimental medicine Vol. 183; no. 1; pp. 329 - 334
• Main Authors: Benatar, T, Carsetti, R, Furlonger, C, Kamalia, N, Mak, T, Paige, C J
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 01.01.1996
• Subjects: Animals; Antigens, CD - metabolism; B-Lymphocytes - immunology; B-Lymphocytes - physiology; Blotting, Western; Calcium - metabolism; CD79 Antigens; Enzyme Activation; Flow Cytometry; Immunoglobulin M - metabolism; Isoenzymes - metabolism; Leukocyte Common Antigens - genetics; Leukocyte Common Antigens - metabolism; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Phenotype; Phospholipase C gamma; Phosphorylation; Precipitin Tests; Receptors, Antigen, B-Cell - metabolism; Signal Transduction; T-Lymphocytes - physiology; Type C Phospholipases - metabolism
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.183.1.329

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.