Tolerance and immunity in antigen-specific B-lymphocyte lines: early receptor binding of either antigen or tolerogen initiates an immune response.
Studies of the effect of tolerance-inducing compounds on B lymphocytes have been complicated by the fact that it is technically difficult to completely isolate the antigen-specific B cell from the effects of T cells or T-cell factors. We have used our cell lines of nonmalignant dinitrophenyl (DNP)-specific B lymphocytes derived from normal mice, which have no contaminating T cells, to study the effect of DNP-murine IgG2a (DNP-MGG), a tolerogen which is not normally immunogenic, on antigen-specific B lymphocytes. Preincubation with DNP-MGG for 48 hr, both in the presence and absence of T-cell factors from EL-4 supernatant prior to adding the antigen DNP-Ficoll, can induce tolerance in cell line B lymphocytes. The suppression is antigen-specific since preincubation with fluorescein-MGG or unconjugated MGG does not suppress the anti-DNP response. At least a 36-hr incubation is required for tolerance induction in B lymphocytes, but a 6-hr preincubation with DNP-MGG augments the immune response to DNP-Ficoll. Lymphocytes incubated for 6 or 24 hr with DNP-MGG prior to adding EL-4 supernatant and filler cells without DNP-Ficoll exhibited an immune response equal to that elicited by DNP-Ficoll and T-cell factors. A 6-hr pulse with a DNP-conjugated polymer of D-glutamic acid and D-lysine (DNP-dGL), a B-cell tolerogen which does not bind to Fc receptors, elicited the same immune response as seen with a 6-hr pulse of DNP-MGG but a 48-hr preincubation with DNP-dGL induced tolerance. Thus, it is likely that the initial binding of the tolerogen to the immunoglobulin receptor on the mature B cell elicits an activation signal similar to that seen with the antigen. The suppressive effect of the tolerogen itself appears to occur at a later stage of the process of the B-cell activation, proliferation, and differentiation.
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D004136:Dinitrobenzenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005362:Ficoll / Q000031:analogs & derivatives / Q000494:pharmacology; D007108:Immune Tolerance / Q000187:drug effects*; D007074:Immunoglobulin G / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009578:Nitrobenzenes / Q000494:pharmacology*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*
C045618:2,4-dinitrophenyl-IgG; C031007:DNP-Ficoll; D004136:Dinitrobenzenes; D007074:Immunoglobulin G; D009578:Nitrobenzenes; D011947:Receptors, Antigen, B-Cell; D005362:Ficoll