Polyclonal activation of immature B cells by preactivated T cells: the role of IL-4 and CD40 ligand.
It is well-established that preactivated CD4+ T cells can activate mature B cells in a polyclonal, MHC-unrestricted fashion. We have used this system to investigate the effects of T cell-derived signals on immature B cells purified from the spleens of neonatal mice, since these cells are unresponsive to many polyclonal activators and are exquisitely sensitive to tolerization. We show that immature B cells can be induced to proliferate by anti-CD3 activated, fixed Th1 and Th2 cells, although the latter induce a greater response than the former. Antibodies to IL-4 partially blocked stimulation by Th2 cells, whereas antibodies to IL-2 and IL-5 had no effect on responses to Th1 cells. This suggested that molecules in addition to IL-4 contribute to the capacity of T cells to induce B cell activation, one likely candidate being the ligand for CD40. We therefore generated mouse erythroleukemia (MEL) transfectants which express CD40 ligand (CD40L). These transfectants also induced proliferation of immature B cells, which is enhanced by IL-4. Unlike the situation with mature B cells, both anti-mu and anti-delta antibodies inhibited the activation of immature B cells by CD40L-MEL cells. However, this inhibition was reversed by IL-4, which synergized with signals delivered through CD40 to render immature B cells refractory to negative signals delivered through sIg. Taken together these data suggest that immature B cells can be activated by T cell-derived contact signals and that CD40L-CD40 interactions, in the presence of IL-4, are capable of abrogating the negative signals generated via sIgM and sIgD receptors expressed by these cells.
Brines
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RD
Laboratory of Cellular Immunology, National Institute for Medical Research, Mill Hill, London, UK.
Klaus
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GG
D000818:Animals; D000831:Animals, Newborn; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001483:Base Sequence; D019013:CD40 Antigens; D023201:CD40 Ligand; D002478:Cells, Cultured; D015847:Interleukin-4 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000941:Antigens; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D015847:Interleukin-4