IN-VITRO INHIBITION BY INTRAVENOUS IMMUNOGLOBULIN OF HUMAN T-CELL-DEPENDENT B-CELL DIFFERENTIATION-INDUCED BY STAPHYLOCOCCAL SUPERANTIGENS

Treatment with intravenous Ig (IVIG) is efficacious not only in humora l immunodeficiency diseases but in several nonimmunodeficiency disorde rs as well, Since microbial superantigens (SAg) have been postulated t o play a role in promoting in vivo pathogenic autoantibody production and since MG preparations are rich in anti-SAg antibodies, we tested w hether MG could inhibit in vitro SAg-driven human T cell-dependent B c ell differentiation. We demonstrate that IVIG inhibits such B cell dif ferentiation 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 cultur es as well, pointing to a SAg-nonspecific inhibitory effect, However, anti-SAg antibodies contained in IVIG can also effect SAg-specific inh ibition, since polyclonal rabbit anti-SAg antisera added early to peri pheral blood mononuclear cell (PBMC) cultures inhibit neither anti-CD3 - nor PWM-driven B cell differentiation and inhibit B cell differentia tion triggered only by the specific SAg against which the individual a ntiserum was raised. Finally, late addition of MG 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 c ells (IgSC). This late inhibition is associated with enhanced SAg-depe ndent cytolytic activity against Raji cell targets which is dramatic i n PBMC cultures but is often not detectable in T + B cell cultures, Re constitution of T + B cell cultures with natural killer cells restores the enhancing capacity of MG on SAg-dependent cytolytic activity as w ell as the late inhibitory effects of IVIG on IgSC generation. Underst anding the multiple mechanisms through which MG can inhibit SAg-driven B cell differentiation may offer a rational basis for determining whi ch patients are likely to favorably respond to MG administration. (C) 1996 Academic Press, Inc.