Major histocompatibility complex-restricted and unrestricted interactions in the T cell-dependent activation of...

The requirements for linked recognition and major histocompatibility complex-restricted interactions in helper T cell-dependent activation of purified unprimed and primed hapten-binding B cells have been investigated. The activation of unprimed hapten-binding B cells required specific antigen and restricted interactions between helper T cells and B cells. As expected, specific hapten-carrier conjugates were essential for the activation of B cells at low antigen doses. Interestingly, however, supraoptimal concentrations (125 micrograms/ml) of carrier protein alone could substitute for specific conjugates in the activation of unprimed B cells. The requirement for restricted helper T cell-B interactions was unchanged under these conditions. These results are discussed in terms of the signalling requirements for B cell activation. In contrast to the results using hapten-specific B cells from unprimed mice, the further stimulation of B cells prepared from mice primed 5 to 7 days earlier with immunogenic forms of the hapten was limited only by the requirements for helper T cell activation. The transition in the activation properties of B cells following in vivo stimulation was not solely a result of the binding of B cell membrane immunoglobulin to specific antigen, since the interaction of unprimed B cells with hapten during their purification, even for extended periods of time, did not alter the requirements for their further stimulation. These results demonstrate that the recent antigenic experience of B cells determines their activation state which, in turn, dictates the further requirements for helper T cell function in B cell stimulation. This implies that specificity of the immune response is determined in the early stages of B cell activation.