The role of interleukin 2 in inducing Ig production in a pokeweed mitogen-stimulated mononuclear cell system.
Cyclosporin A (CsA) has been found previously to block mitogen-stimulated T cell proliferation and production of discrete T cell-derived lymphokines such as interleukin 2 (IL 2) and interferon (IFN)-gamma. In addition, CsA blocks pokeweed mitogen (PWM)-driven T cell-dependent differentiation of B cells into immunoglobulin (Ig)-secreting cells. Recently, we reported that CsA (1 microgram/ml) inhibited PWM-induced T cell production of IL 2 and IFN-gamma, but supernatants retained B cell differentiation factor (BCDF)-like activity. The present study demonstrates the ability of CsA to suppress T cell functions in PWM-driven Ig production in mononuclear cells (MNC), and the capacity of exogenous T cell lymphokines to reverse CsA-induced suppression. CsA profoundly suppressed PWM-driven PFC formation (greater than 95%). However, Ig production was substantially reconstituted by the addition of IL 2 at concentrations of 10 to 50 U/ml. In contrast, no effects were observed by the addition of IFN-gamma or BCGF. The kinetics of CsA inhibition of Ig production and IL 2 secretion were found to be closely related. In addition, to obtain effective reconstitution in the CsA-treated PWM-MNC system it was necessary to add IL 2 at the initiation of culture. T cells themselves were also required for B cell differentiation in this system. However, surface Ig+ cells obtained by cell sorting after 3 days of culture could differentiate in the absence of T cells but only in response to IL 2, not in response to IFN-gamma or BCDF. Thus, in PWM-driven B cell differentiation T cells are necessary early in culture, whereas IL 2 is essential from the initial stage of B cell activation through the final stage of B cell differentiation.
D000328:Adult; D001402:B-Lymphocytes / Q000166:cytology; D002450:Cell Communication; D002454:Cell Differentiation / Q000187:drug effects; D003524:Cyclosporins / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000032:analysis / Q000502:physiology*; D015847:Interleukin-4; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D008222:Lymphokines / Q000494:pharmacology; D011043:Pokeweed Mitogens / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000502:physiology
D003524:Cyclosporins; D006133:Growth Substances; D007136:Immunoglobulins; D007376:Interleukin-2; D008222:Lymphokines; D011043:Pokeweed Mitogens; D015847:Interleukin-4; D007371:Interferon-gamma