Inhibition of pokeweed mitogen-induced Ig secretion by IgG monoclonal antibodies to MHC class I and class II molecules requires binding of the intact antibody.
Seven purified IgG monoclonal antibodies reactive with different epitopes on DQw1, DR, HLA-A3 or p85 glycoprotein of human lymphocytes have each been shown to inhibit pokeweed mitogen (PWM)-induced IgG and IgM secretion in a dose-dependent manner. Binding of these antibodies to their target antigens was required for the suppression. Antibodies of IgG1, IgG2 alpha, and IgG2b subclasses were able to inhibit both IgG and IgM secretion in the PWM system. The mechanisms by which two of the monoclonal antibodies (MoAbs)-77.34, specific for the class II antigen DQw1, and GAP A3, specific for the class I antigen HLA-A3-caused inhibition--were analyzed. The suppressive effects of 77.34 and GAP A3 were maximal when added at the initiation of the culture period. No inhibition of IL-2 production or cellular proliferation was detected. Supernatants obtained from inhibited cultures were not themselves suppressive. The F(ab')2 fragments of either 77.34 or GAP A3 failed to influence PWM-Ig secretion, indicating that intact IgG molecules were required. This suggests that the observed inhibition might be mediated via Fc receptors. Together F(ab')2 fragments of either 77.34 or GAP A3 and a control IgG2a protein did not reconstitute the inhibitory effects of intact 77.34 or GAP A3. Suppression, therefore, required intact Fc portions on the same IgG molecules as those that bound to DQw1 or HLA-A3. These studies suggest that populations of IgG molecules that crosslink sufficient numbers of Fc receptors with other cell surface antigens on peripheral blood mononuclear cells (PBMs) during the early stages of B-cell activation can inhibit Ig secretion. Crosslinking of B-cell Fc receptors with SIg has been proposed by others to act as a negative signal for Ig production; our data raise the possibility that crosslinking of FcR with B-cell plasma membrane components other than SIg can also suppress Ig secretion.
Pulleyblank
B M
BM
Department of Immunology, University of Toronto, Ontario, Canada.
Nakhooda
A F
AF
Letarte
M
M
Falk
J A
JA
D000328:Adult; D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D006681:HLA-D Antigens / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G; D007136:Immunoglobulins / Q000096:biosynthesis*; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D011043:Pokeweed Mitogens / Q000494:pharmacology; D011961:Receptors, Fc / Q000276:immunology; D017452:Receptors, IgG; D016201:Receptors, Lymphocyte Homing
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D006023:Glycoproteins; D006680:HLA Antigens; D006681:HLA-D Antigens; D007074:Immunoglobulin G; D007136:Immunoglobulins; D011043:Pokeweed Mitogens; D011961:Receptors, Fc; D017452:Receptors, IgG; D016201:Receptors, Lymphocyte Homing