Activation of antigen-specific B cells: role of T cells, cytokines, and antigen in induction of growth and differentiation.

T cells and cytokines were used to activate highly enriched populations of 2,4,6-trinitrophenyl (TNP)-binding B cells (TNP-ABC). TNP-ABC did not proliferate or differentiate when they were cultured with thymus-dependent (TD) antigen, even in the presence of supernatants known to contain B-cell growth and differentiation factors. However, purified TNP-ABC did proliferate and differentiate when they were cultured with TD antigen in the presence of carrier-primed T cells and antigen (TNP-keyhole limpet hemocyanin)--i.e., linked recognition. TNP-ABC blasts generated under conditions of linked recognition proliferated and differentiated in response to cytokines in the absence of T cells and antigen. In contrast, under conditions of nonlinked recognition (hapten and carrier on different molecules) TNP-ABC blasts also proliferated but did not differentiate in response to the same cytokines. These results indicate that antigen-specific "resting" B cells must be activated by T cells and antigen prior to becoming responsive to cytokines. Furthermore, activation under conditions of linked and nonlinked recognition generates two different types of blasts with regard to their subsequent response to cytokines.