An essential role for interleukin 1 and a dual function for interleukin 2 in the immune response of murine B lymphocytes to sheep erythrocytes.

The macrophage-derived lymphokine interleukin 1 (IL-1) and the T cell-derived lymphokine interleukin 2 (IL-2) help B lymphocytes to generate antibodies against sheep erythrocytes in vitro. It has been difficult to determine whether these factors act on antigen-reactive B cells directly or via accessory cells, since it is not technically feasible to prepare completely homogenous cell populations. Therefore we examined the question of lymphokine action on B cells using an indirect approach. First we determined effects of the two factors in the phenotypic differentiation assay, a short-term culture of cloned B cells certainly free of accessory cells. Next, we investigated whether the effects seen in this assay could be related to results obtained in the long-term (four-day) assay of antibody production. Interleukin 1 induced cloned 70Z/3 B lymphocytes to express new cell surface markers in the phenotypic B cell differentiation assay. IL-2 rendered these B cells refractory to differentiation caused by IL-1. In the antibody production assay, IL-1 controlled, as was shown previously, an early phase of the response in which B cells become responsive to T cell-derived helper factors. In order to demonstrate the requirement for IL-1, it was necessary to rigorously prevent endogenous IL-1 production. Synergy between IL-1 and IL-2 was observed when IL-2 was given as late as day 2 of a four-day culture period. This synergy was seen over a broad dose range of IL-2 (10-1,000 U/ml). However, IL-2, when added in high concentrations (200-1,000 U/ml) during the early (IL-1-dependent) phase of the B cell response inhibited antibody production.(ABSTRACT TRUNCATED AT 250 WORDS)