THE ROLE OF INTERLEUKIN-4 IN SPECIFIC ANTIBODY-RESPONSES BY HUMAN B-CELLS

This study was designed to investigate the requirement for interleukin 4 (IL-4) in specific antibody responses by human lymphocytes. Addition of IL-4 to antigen (influenza virus)-stimulated cultures of tonsillar mononuclear cells was found to suppress specific antibody production significantly at doses as low as 10 units/ml. Specific immunoglobulin (IgG), IgA, and IgM antibodies were all equally inhibited by IL-4. Inhibition of the antibody response with IL-4 was completely abrogated by an IL-4 blocking antibody showing that the effect was specific for IL-4. It was also found that anti-IL-4 did not inhibit specific antibody production, showing that IL-4 was not required for responses to antigen. In contrast, significant inhibition was obtained with anti-Tac, indicating an important role for lL-2. In the absence of T helper cells antibody responses to influenza virus were completely restored with T cell replacing factor [TRF; lL-2 or low-molecular-weight B cell growth factor (BCGF(low))], but not with lL-4. In fact, lL-4 significantly suppressed the antibody response obtained when either lL-2 or BCGF(low) was used as a TRF. Addition of lL-4 at different times after in vitro stimulation with antigen and lL-2 showed that the inhibitory activity of lL-4 was maximal during the first 3 days of culture and was lost by day 4. lL-4 therefore seems to inhibit an early activation event (possibily dependent on lL-2 or BCGF(low)), or B cell proliferation essential for specific responses to antigen. Taken together, these observations show that lL-4 is not required for all specific antibody responses by human B cells and add support to the possibility that this cytokine is important in suppression.