The roles of interleukin 2 and interferon‐γ in human B cell activation, growth and differentiation

The roles of interleukin 2 (IL 2) and interferon‐γ (IFN‐γ) 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‐γ, by contrast, could not support either response alone. When a twostep 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‐γ. However, the presence of T sup, rIL 2, or rIFN‐γ 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‐γ 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‐γ. The results emphasize the role of specific T cell factors in determining the outcome of humoral immune responses.