Control of primary and secondary antibody responses by cytotoxic T lymphocytes specific for a soluble antigen

BALB/c mice immunized with keyhole limpet hemocyanin (KLH) develop Thy‐1⁺ and CD8⁺, KLH‐specific cytotoxic T cells (T_c). Such T_c cells can lyse TNP‐specific B cells activated with TNP‐KLH, but not with TNP‐ovalbumin. Cytotoxicity was inhibited by anti‐H‐2K/D antibodies, but not by anti‐Ia antibodies, suggesting a major histocompatibility complex class I‐restricted killing. Selective enrichment for virgin and memory TNP‐specific B cells revealed that the latter cells were relatively resistant to lysis by KLH‐specific T_c cells. Depletion of CD8⁺ T cells from cultures of TNP‐specific virgin B cells activated with TNP‐KLH and KLH‐primed T cells, increased the titer of anti‐TNP antibodies in the culture supernatants. This increase was reduced if KLH‐primed CD8⁺ T cells were added to the culture 1 day before its termination. Anti‐TNP antibody secretion by memory B cells activated in the same manner was not affected by depletion or addition of CD8⁺ cells. These results suggest that T_c cells are generated following immunization with a soluble antigen which may participate in the down‐regulation of primary B cell responses.