Molecular Control of B Cell Triggering by Antigen-Specific T Cell-Derived Helper Factor

Abstract

Abstract Soluble, carrier-specific helper factor extracted from thymus-derived (T) cells primed to the carrier in vivo has been used to analyze the relationship between the degree of T cell help required to stimulate a primary antibody response in vitro and the molecular structure of the antigen. In order to define the conditions for optimal T cell help, we have constructed antigenic probes which consist of a number of serum proteins conjugated to a carbohydrate backbone. When these probes were trinitrophenylated for use as hapten-carrier conjugates to stimulate in vitro anti-TNP immune responses, we were able to define the conditions for optimal T cell help as one at which the carrier antigenic determinants are presented to the bone marrow-derived (B) cell in a closely spaced sequence. We suggest such a carrier focuses helper factor molecules by providing an array of determinants to which they can bind and then interact in a concentrated fashion with a small area of the B cell surface membrane. When comparing the capacity of B cells to cooperate with helper factor from either syngeneic or allogeneic T cells, it was found that for a successful immune response to occur, both cooperating elements have to be of syngeneic origin. This extends the concept of allogeneic restriction between cooperating B and T cells to the level of interaction of soluble T cell-derived helper factor with B cells.