Parameters of tolerance induction by antigen targeted to B lymphocytes
Biochemistry & Molecular Pharmacology
Graduate School of Biomedical Sciences; Department of Molecular Genetics and Microbiology
Medical Subject Headings
Animals; *Antibody Formation; B-Lymphocytes; Female; *Immune Tolerance; Immunoglobulin D; Lymphocyte Activation; Mice; Mice, Inbred Strains; Receptor Aggregation; Receptors, Antigen, B-Cell; T-Lymphocytes
Life Sciences | Medicine and Health Sciences
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.
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Citation: J Immunol. 1993 Sep 15;151(6):2958-64.
Journal of immunology (Baltimore, Md. : 1950)
Eynon, Elizabeth E. and Parker, David C., "Parameters of tolerance induction by antigen targeted to B lymphocytes" (1993). GSBS Student Publications. 274.