TY - JOUR
T1 - CD38 expression in early B-cell precursors contributes to extracellular signal-regulated kinase-mediated apoptosis
AU - Romero-Ramírez, Héctor
AU - Morales-Guadarrama, Monserrat Teresa
AU - Pelayo, Rosana
AU - López-Santiago, Rubén
AU - Santos-Argumedo, Leopoldo
N1 - Publisher Copyright:
© 2014 John Wiley & Sons Ltd.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - 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.
AB - 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.
KW - Bone marrow
KW - CD38
KW - Extracellular signal-regulated kinase
KW - Mouse B-cell development
UR - http://www.scopus.com/inward/record.url?scp=84922563755&partnerID=8YFLogxK
U2 - 10.1111/imm.12370
DO - 10.1111/imm.12370
M3 - Artículo
SN - 0019-2805
VL - 144
SP - 271
EP - 281
JO - Immunology
JF - Immunology
IS - 2
ER -