| Abstract: | Although adult murine B cells can be stimulated to proliferateby IgM receptor cross-linking, we and others have shown thatthese cells will undergo apoptosis in vitro in a dose-, time-and temperature-dependent manner with polyclonal but not monoclonalantl-lgM. To test the role of c-myc and cell cycle progressionin B cell apoptosis, we examined normal, Sp6 antl-TNP Ig andEµ-myc transgenic splenocytes for receptor-mediated apoptosisin vitro. In normal mice, both spontaneous and anti-lgM-lnducedprogrammed cell death were specifically blocked by antisenseoligodeoxynucleotides for the c-myc proto-oncogene, whereasnonsense myc oligonucleotides and irrelevant oligonucleotideshad only a minor effect. Similarly, TNP-dextran-induced apoptosisin Sp6 antl-TNP transgenics was inhibited by antisense c-myc.This effect was not due to the mitogenic effects of unmethylatedCpG-contalnlng sequences because ones lacking this motif, aswell as methylated oligonucleotides containing this motif, preventedapoptosis, and mitogenic doses of lipopolysaccharlde failedto Inhibit anti-lgM-driven cell death. Importantly, antisensec-myc also prevented the anti-lgM-lnduced increase in myc proteinspecies. Moreover, spontaneous apoptosis in vitro was exaggeratedin Eµ-myc transgenic B cells. To examine the role of CD45in anti-lgM-induced apoptosis, we treated spleen cells fromCD45 knockout mice, which do not proliferate with anti-IgM,and found that B cells from these underwent apoptosis normallydespite the lack of entry into S. These data suggest that anti-IgMdriven apoptosis does not require CD45. Rather, apoptosis maybe due to an overexpression of myc protein in the absence ofsignals which can drive B cells productively Into S, but thefailure to proliferate normally is insufficient for apoptosisto occur. |
