CD72 ligation regulates defective naive newborn B cell responses.
The biological basis for reduced Ig production by naive newborn B cells compared to adult peripheral blood B cells is not fully understood. In a Con A + IL-2 T cell-dependent system using "competent" adult T cells, adult B cells produced large amounts of IgM, IgG, and IgA, while cord B cells were restricted to low levels of only IgM production. Cord B cell activation was also diminished. The contribution of specific B-T cell contact-mediated events to the diminished cord B cell response in this system, using mAbs to CD40, CD28, CD80, and CD72, were investigated, as well as regulation of B cell Ig production by cytokines. alphaCD72 ligation increased cord B cell activation and IgM production, but did not affect adult B cells. Blocking alphaCD40 mAb inhibited cord B cell Ig production completely, but only partly inhibited adult B cell Ig production even at high concentration, suggesting a greater sensitivity of cord B cells to disruption of the CD40-CD40L interaction. Addition of IL-10 did not increase cord B cell Ig production, while adult B cell Ig production was increased. However, combined addition of IL-10 and alphaCD72 significantly increased cord B cell Ig production over that in the presence of either alphaCD72 or IL-10 alone, but had no effect on adult B cells over that of IL-10 alone. These data suggest that the diminished T cell-dependent response of cord B cells is due to reduced or absent CD72 ligation. CD72 ligation plays an important role in the induction of primary responses by naive B cells. CD72 modulation of naive B cell sensitivity to IL-10 stimulation may have implications in the induction of class switch, which is deficient in newborn B cells. Since all T cells express CD5 constitutively, these data also suggest the existence of another ligand for CD72.
Howard
L M
LM
Children's Research Centre, Our Lady's Hospital for Sick Children, Crumlin, Dublin, Ireland.
Reen
D J
DJ
D000328:Adult; D000375:Aging / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003208:Concanavalin A / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D005312:Fetal Blood / Q000166:cytology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C064228:CD72 protein, human; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D003208:Concanavalin A; D016753:Interleukin-10