title: In vitro inhibition by intravenous immunoglobulin of human T cell-dependent B cell differentiation induced by staphylococcal superantigens.
abstract: Treatment with intravenous Ig (IVIG) is efficacious not only in humoral immunodeficiency diseases but in several nonimmunodeficiency disorders as well. Since microbial superantigens (SAg) have been postulated to play a role in promoting in vivo pathogenic autoantibody production and since IVIG preparations are rich in anti-SAg antibodies, we tested whether IVIG could inhibit in vitro SAg-driven human T cell-dependent B cell differentiation. We demonstrate that IVIG inhibits such B cell differentiation by at least three different mechanisms. Early addition of IVIG inhibits B cell differentiation not only in SAg-stimulated PBMC cultures but in anti-CD3- and pokeweed mitogen (PWM)-stimulated cultures as well, pointing to a SAg-nonspecific inhibitory effect. However, anti-SAg antibodies contained in IVIG can also effect SAg-specific inhibition, since polyclonal rabbit anti-SAg antisera added early to peripheral blood mononuclear cell (PBMC) cultures inhibit neither anti-CD3- nor PWM-driven B cell differentiation and inhibit B cell differentiation triggered only by the specific SAg against which the individual antiserum was raised. Finally, late addition of IVIG at a time at which B cells have already committed to terminal differentiation inhibits SAg-driven, but not anti-CD3- or PWM-driven, generation of Ig-secreting cells (IgSC). This late inhibition is associated with enhanced SAg-dependent cytolytic activity against Raji cell targets which is dramatic in PBMC cultures but is often not detectable in T + B cell cultures. Reconstitution of T + B cell cultures with natural killer cells restores the enhancing capacity of IVIG on SAg-dependent cytolytic activity as well as the late inhibitory effects of IVIG on IgSC generation. Understanding the multiple mechanisms through which IVIG can inhibit SAg-driven B cell differentiation may offer a rational basis for determining which patients are likely to favorably respond to IVIG administration.
authors.affiliation: Department of Medicine, University of Southern California School of Medicine, Los Angeles 90033, USA.
authors.forename: W
authors.initials: W
authors.lastname: Stohl
authors.forename: J E
authors.initials: JE
authors.lastname: Elliot
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004306:Dose-Response Relationship, Immunologic; D004768:Enterotoxins / Q000494:pharmacology; D006462:Hemolytic Plaque Technique; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008211:Lymphocyte Cooperation / Q000187:drug effects*; D011043:Pokeweed Mitogens / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D004768:Enterotoxins; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D011043:Pokeweed Mitogens; D018089:Superantigens; C031818:enterotoxin B, staphylococcal; C034959:enterotoxin C, staphylococcal