TY - JOUR
T1 - Immunoglobulin-mediated signal transduction in B cells from CD45-deficient mice
AU - Benatar, Tania
AU - Carsetti, Rita
AU - Furlonger, Caren
AU - Kamalia, Nilupa
AU - Mak, Tak
AU - Paige, Christopher J.
PY - 1996/1/1
Y1 - 1996/1/1
N2 - 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 hydrolysis 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 cross-linking. 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 IgD(hi), IgM(lo) phenotype. Although both the basal and anti-Ig-induced levels of phosphorylation of Ig-α and phospholipase Cγ2 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.
AB - 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 hydrolysis 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 cross-linking. 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 IgD(hi), IgM(lo) phenotype. Although both the basal and anti-Ig-induced levels of phosphorylation of Ig-α and phospholipase Cγ2 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.
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U2 - 10.1084/jem.183.1.329
DO - 10.1084/jem.183.1.329
M3 - Article
C2 - 8551241
AN - SCOPUS:0030070349
VL - 183
SP - 329
EP - 334
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 1
ER -