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In this report we demonstrate a striking relationship between CD38\u2010mediated mitogenesis and the ability of surface IgM to promote B cell proliferation. Tolerized B lymphocytes obtained from a double\u2010transgenic mouse model of B cell tolerance do not proliferate in response to antigen stimulation through the Ig receptor or to agonistic anti\u2010CD38 antibodies. Similarly, B\u20101 cells isolated from the peritoneal cavity of normal mice, and splenic B cells isolated from newborn mice were also unresponsive to both anti\u2010IgM and anti\u2010CD38 stimulation. All of these CD38\u2010unresponsive B cells expressed normal levels of cell surface CD38 and responded to numerous other stimuli. CD38 immunoprecipitated from these B cell populations was normal in size and effectively hydrolyzed NAD, suggesting that the defect in CD38 signaling likely occurs downstream of CD38 itself. Signaling through CD38 and IgM does not always have identical effects on B cells since anti\u2010CD38 cannot deliver inhibitory growth or differentiation signals to normal B cells or immature B cell lines. Nevertheless, the correlative data with these multiple B cell models of unresponsiveness suggests that the signaling pathway utilized by CD38 and IgM intersect, possibly sharing at least one of the crucial components of the Ig receptor signaling cascade.<\/jats:p>","DOI":"10.1002\/eji.1830250531","type":"journal-article","created":{"date-parts":[[2007,3,2]],"date-time":"2007-03-02T01:07:04Z","timestamp":1172797624000},"page":"1338-1345","source":"Crossref","is-referenced-by-count":32,"title":["Signaling through murine CD38 is impaired in antigen receptor\u2010unresponsive B cells"],"prefix":"10.1002","volume":"25","author":[{"given":"Frances E.","family":"Lund","sequence":"first","affiliation":[]},{"given":"Nanette W.","family":"Solvason","sequence":"additional","affiliation":[]},{"given":"Michael P.","family":"Cooke","sequence":"additional","affiliation":[]},{"given":"Andrew W.","family":"Heath","sequence":"additional","affiliation":[]},{"given":"J. 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