CD 38 expression in early B ‐cell precursors contributes to extracellular signal‐regulated kinase‐mediated apoptosis

Summary CD38 is a 45 000 molecular weight transmembrane protein that is expressed in immature and mature lymphocytes. However, the expression and function of CD 38 during B ‐cell differentiation in mice is poorly understood. Here, we report that CD 38 is expressed from the earliest stages of B ‐cell development. Pre‐pro‐ B , pro‐ B , pre‐ B and immature B cells from murine bone marrow all stained positive for CD 38. Interestingly, CD 38 expression increases with B ‐cell maturation. To assess the role of CD 38 during B ‐cell maturation, CD 38‐deficient mice were analysed. CD 38 −/− mice showed a significant increase in both the frequency of B ‐lineage cells and the absolute numbers of pre‐pro‐ B cells in bone marrow; however, no other differences were observed at later stages. CD 38 cross‐linking in B a/ F 3 cells promoted apoptosis and marked extracellular signal‐regulated kinase ( ERK ) phosphorylation, and these effects were reduced by treatment with the mitogen‐activated protein kinase/ ERK kinase inhibitor PD 98059, and similar effects were observed in B ‐cell precursors from bone marrow. These data demonstrate that B ‐cell precursors in mouse bone marrow express functional CD 38 and implicate the early ligation of CD 38 in the ERK ‐associated regulation of the B ‐lineage differentiation pathway.