Cellular mechanisms in the in vitro inhibition of pokeweed mitogen-induced B cell differentiation by immunoglobulin for intravenous use.
Polyspecific monomeric IgG for i.v. use (IgSRK; Sandoglobulin) can inhibit in vitro pokeweed mitogen (PWM)-induced B cell differentiation. This antigen-nonspecific inhibition is an early event, because removal of the IgSRK from cultures of PWM-stimulated peripheral blood mononuclear cells (PBMC) after as short a period as 24 hr could not reverse the inhibitory effects. Furthermore, replacement of the IgSRK-exposed T cells after 48 hr of culture with fresh autologous T cells could not abrogate the inhibition. In addition, IgSRK exerted an inhibitory effect on non-T cells even before their activation by PWM. Neither augmentation of T suppressor activity nor inhibition of T helper activity could be demonstrated as a consequence of interaction with IgSRK. Irradiation of the T cells before culture, supplementing the culture medium with exogenous interleukin 2, monocyte depletion, or depletion of the Leu-11+ population had no effect on the IgSRK-mediated inhibition. Tonsil cells were as susceptible to the inhibitory effects of IgSRK as were unseparated PBMC. Taken together, these experiments point to a direct inhibitory effect of IgSRK on the B cell in this antigen-nonspecific system. However, minor roles for monocytes, T cells, and/or Leu-11+ cells cannot be excluded. This inhibitory capacity of IgSRK might be efficacious clinically in the treatment of autoimmune disorders in which pathogenic autoantibodies play a role. However, such treatment might also inhibit desired antibody responses to vaccinations and/or infectious agents.
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D002469:Cell Separation; D002478:Cells, Cultured; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology*; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents / Q000502:physiology*; D008213:Lymphocyte Activation; D009000:Monocytes; D014066:Palatine Tonsil / Q000166:cytology; D011043:Pokeweed Mitogens / Q000494:pharmacology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D011043:Pokeweed Mitogens