Roles of IL-2 and antigen in the later stages of the primary antibody response.

Spleen cells, obtained 2-5 days after in vivo priming with sheep erythrocytes (SRBC), were cultured to determine the presence of plaque-forming cell (PFC) precursors capable of developing into mature PFC under the influence of various stimulants. Lipopolysaccharide (LPS), added together with SRBC at the initiation of a 48-hr in vitro culture, enhanced the PFC response of primed spleen cells. In vivo priming for a minimum of 3 days was required, and maximal numbers of PFC were obtained from spleen cells primed for 4 days. Depletion of T lymphocytes from Day 3-primed spleen cells abrogated LPS-mediated enhancement, and addition of concanavalin A supernatants to the T-cell depleted system restored the enhancement, suggesting that LPS action required co-operation with a product(s) of activated T cells. Addition of various interleukin-2 preparations including recombinant human IL-2 to the system restored the LPS-mediated enhancement. The response of Day 3 cells from which T cells were eliminated as vigorously as possible was similarly restored by the addition of IL-2, LPS and antigen, suggesting that IL-2 reacts directly with PFC precursors that have developed IL-2 receptors. LPS-mediated enhancement, in the presence or absence of T cells, was also markedly dependent on the presence of SRBC during in vitro culture. These data suggest that, in co-operation with IL-2 and other co-factors, antigen plays a significant role in driving the later stages of differentiation and/or division of PFC precursors to mature PFC.