title: CD38 expression in early B-cell precursors contributes to extracellular signal-regulated kinase-mediated apoptosis.
abstract: CD38 is a 45,000 molecular weight transmembrane protein that is expressed in immature and mature lymphocytes. However, the expression and function of CD38 during B-cell differentiation in mice is poorly understood. Here, we report that CD38 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 CD38. Interestingly, CD38 expression increases with B-cell maturation. To assess the role of CD38 during B-cell maturation, CD38-deficient mice were analysed. CD38(-/-) 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. CD38 cross-linking in Ba/F3 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 PD98059, 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 CD38 and implicate the early ligation of CD38 in the ERK-associated regulation of the B-lineage differentiation pathway.
authors.affiliation: Department of Molecular Biomedicine, Centre for Research and Advanced Studies (CINVESTAV-IPN), Mexico City, Mexico; Department of Immunology, National School of Biological Sciences, IPN, Mexico City, Mexico.
authors.forename: Héctor
authors.initials: H
authors.lastname: Romero-Ramírez
authors.forename: Monserrat Teresa
authors.initials: MT
authors.lastname: Morales-Guadarrama
authors.forename: Rosana
authors.initials: R
authors.lastname: Pelayo
authors.forename: Rubén
authors.initials: R
authors.lastname: López-Santiago
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Santos-Argumedo
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D019070:Cell Lineage / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology
chemical_list: D005419:Flavonoids; D008562:Membrane Glycoproteins; D047428:Protein Kinase Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; C498155:Cd38 protein, mouse; D051997:ADP-ribosyl Cyclase 1; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: CD38; bone marrow; extracellular signal-regulated kinase; mouse B-cell development