The roles of interleukin 2 and interferon-gamma in human B cell activation, growth and differentiation

The roles of interleukin 2 (IL 2) and interferon-gamma (IFN-gamma) in human peripheral blood B cell activation, growth and differentiation were examined. Highly purified B cells stimulated with Cowan I Staphylococcus aureus (SA) proliferated minimally and generated no immunoglobulin-secreting cells (ISC) without the addition of T cell supernatants (T sup) produced by mitogen-activated T cells. Recombinant IL 2 (rIL 2) alone was able to promote maximum proliferation and generation of ISC in cultures of highly purified SA-stimulated B cells when present from the initiation of the incubation. IFN-gamma, by contrast, could not support either response alone. When a two-step culture system was employed to determine the effect(s) of T cell influences during both initial activation and in propagating the response following activation, it was found that B cells activated by SA alone subsequently responded maximally to T sup but only minimally to IL 2 and not at all to IFN-gamma. However, the presence of T sup, rIL 2, or rIFN-gamma during initial activation with SA was found to facilitate greatly the subsequent capacity of the activated B cells to proliferate and differentiate in response to either T sup or IL 2. These data suggest two distinct pathways of human B cell responsiveness. Activities in T sup other than IL 2 or IFN-gamma can support the growth and differentiation of B cells initially activated with SA alone, whereas rIL 2 is capable of promoting these responses maximally only when B cells have been initially activated by SA in the presence of T cell lymphokines, such as IL 2 or IFN-gamma. The results emphasize the role of specific T cell factors in determining the outcome of humoral immune responses.