Human B cell precursors proliferate and express CD23 after CD40 ligation.
The CD40 surface membrane molecule plays an important role in the activation of mature human B cells, but its role in earlier stages of B lineage development is unknown. Here, we have investigated the effects of triggering the CD40 antigen on B cell precursors (BCP) by crosslinking with anti-CD40 antibody presented by Fc gamma-receptor type II-transfected murine Ltk- cells (CD40 system). CD10+ surface immunoglobulin negative (sIg-) BCP, freshly isolated from fetal bone marrow or precultured on stromal cells, proliferated in the CD40 system. This effect required the presence of IL-3, which acted as a specific cosignal among a panel of cytokines examined. The association of IL-10 and IL-7 potentiated the observed IL-3 and CD40-dependent BCP proliferation, demonstrating that IL-10 can act on early B lineage cells. CD40-dependent activation of fetal BCP did not favor maturation to sIg+ B cells, but resulted in the induction of high levels of surface membrane CD23. The emerging CD23+ BCP lacked sIg and CD10, and represented an important proportion of the cycling cells in the CD40-dependent cultures. Taken together, our data demonstrate that stimulation of the CD40 antigen induces expression of the CD23 gene, and regulates cell proliferation during normal human B cell ontogeny.
Saeland
S
S
Schering-Plough Laboratory for Immunological Research, Dardilly, France.
Duvert
V
V
Moreau
I
I
Banchereau
J
J
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens; D002478:Cells, Cultured; D005260:Female; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D015260:Neprilysin / Q000032:analysis; D011247:Pregnancy; D017464:Receptors, Complement 3d / Q000032:analysis; D017455:Receptors, IgE / Q000032:analysis*
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D007377:Interleukin-3; D017464:Receptors, Complement 3d; D017455:Receptors, IgE; D015260:Neprilysin