H‐2‐restricted T‐B cell interactions involved in polyspecific B cell responses mediated by soluble antigen

Abstract

Abstract Maturation of polyspecific B cells to Ig secretion was induced in response to the interaction of helper T cells with soluble antigen. The in vitro propagated, keyhole limpet hemocyanin (KLH)‐primed C57BL16 T cells used in these experiments proliferated in response to antigen presented on I‐A‐compatible antigen‐presenting cells and were depleted of alloreactive cells. These T cells induced a strong polyspecific plaque‐forming cell response from normal C57BL/6 B cells over a wide range of KLH concentrations (100 μg/ml to 0.01 μg/ml). Culture conditions were established whereby H‐2‐restricted T cell‐macrophage interactions were nonlimiting, allowing a direct analysis of H‐2‐restricted T‐B cell interactions involved in polyspecific B cell induction. The requirements for B cell induction/amplification were dependent on the size of the responding B cell population. Small B cells were activated only at high concentrations of KLH and required a direct H‐2‐restricted interaction with KLH‐primed helper T cells. In contrast, large B cells were induced/amplified over the full range of KLH concentrations tested in an H‐2‐unrestricted manner, limited only by the H‐2‐restricted, antigen‐dependent activation of T helper cells. The requirement for high antigen concentration in the activation of small B cells is proposed to reflect a requirement for antigen binding to the B cell surface via nonspecific interactions. This binding was not in itself stimulatory, but expression of antigen in conjunction with B cell surface Ia antigens provided a focus for a direct interaction with Ia‐restricted, antigen‐specific T helper cells (or factors). In contrast, the H‐2‐unrestricted induction/ amplification of large B cells was mediated solely as a consequence of the helper T cell activation which occurred at the lowest concentrations of KLH tested. T helper cell activation is proposed to lead to the production of non‐antigen‐specific, non‐Ia‐restricted factors supporting the continued growth of blasted B cells. Thus, while an H‐2‐restricted T cell‐macrophage interaction is an obligate requirement for polyspecific B cell responses, the requirement for a direct H‐2‐restricted T‐B cell interaction varies with the pre‐existing state of activation of the responding B cell population.