Parameters of tolerance induction by antigen targeted to B lymphocytes.
We have shown that a foreign protein Ag (the F(ab) fragment of rabbit IgG) becomes a particularly effective tolerogen when it is targeted to B lymphocytes in vivo. This is done by injecting the Ag intravenously into mice in the form of the F(ab) fragment of rabbit anti-mouse IgD antibody (F(ab)) rabbit anti-delta). Our hypothesis is that resting B cells are tolerogenic APC for CD4+ T cells in unprimed animals, and induce Ag-specific nonresponsiveness in the Th cell compartment by presenting Ag without appropriate costimulatory signals. In this report, we find that Ag-activated T cells appear to be resistant to tolerance induction, because F(ab) rabbit anti-delta given 5 days after challenge with rabbit F(ab) in alum adjuvant has little or no effect of the subsequent antibody response. Tolerance also fails in this model when B cells are activated independently of Ag by simultaneous injection of activating concentrations of divalent, IgG mouse anti-delta at the same time as F(ab) rabbit anti-delta. Finally, nonresponsiveness in the T cell compartment is not limited to a lesion in T cell help for the antibody response, because T cells from mice treated with F(ab) rabbit anti-delta and then primed with rabbit F(ab) fragments in CFA show reduced T cell proliferation and IL-2 production when restimulated with Ag in vitro.
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester 01655.
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Parker
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D007108:Immune Tolerance; D007072:Immunoglobulin D / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D011940:Receptor Aggregation; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology
D007072:Immunoglobulin D; D011947:Receptors, Antigen, B-Cell