B cell responses to a peptide epitope: III. Differential T helper cell thresholds in recruitment of B cell fine specificities

Th cell requirements in the individual stages comprising a murine humoral response to a synthetic peptide were examined. Induction of a T-dependent IgM response was readily achieved in the presence of unprimed or low numbers of Ag-primed T cells. In contrast, class switch to the IgG isotype of Abs demanded a markedly elevated frequency of primed T cells and occurred concomitantly with B cell differentiation into an membrane-bound IgG+ memory population. These results indicated that induction and progression of a T-dependent humoral IgG response were comprised of a single rate-limiting step represented by that involving Ab isotype switch. Subsequent studies established that this also represented the principal step where antibody-purifying mechanisms operate. This was enforced by imposing a threshold barrier for Th cell recruitment by early Ag-activated B cells to enable class switch and consequent retention as the response progresses. The quantum of this threshold, however, was not invariant, but, rather, was described as a balance between the affinity of B cell receptor for Ag and the frequency of Ag-specific Th cells.