REGULATION OF THE SPECIFIC PLAQUE-FORMING CELL RESPONSE IN MAN - RESTRAINT OF B-CELL RESPONSIVENESS

Specific in vitro plaque‐forming cell (PFC) responses of normal human lymphocytesare antigen dose‐dependent, with bell‐shaped dose response patterns. Both the bell‐shaped antigen dose response characteristics as well as optimal PFC responseamplitudes are dictated by two distinct and separable T lymphocyte subpopulationswhich act on a nonlimiting set of PFC precursor B cells. Specific theophylline‐sensitive suppressor and theophylline‐resistant helper T cells are activated by antigen in adose‐dependent fashion. The initially small suppressor cell pool expands exponentially following antigen contact, whereas the larger helper cell population does not. This leaves a restricted range of antigen concentrations where net helper activity issufficient to promote a PFC response. Due to coinduced suppressor activity, PFCresponses showed an overall negative restraint at all antigen concentrations. Limitingdilution analysis suggested that it is the numerical balance between the two alternative T cell subsets which determines the extent of this negative restraint. These datadelineate a cellular mechanism for the translation of an antigenic stimulus into a B cellantibody response; theophylline‐sensitive suppressor cells are able to expand inresponse to this stimulus and represent the main regulative vector. Thus, in mixedlymphocyte populations, antigen concentration is a valuable probe for studies of thebalance of discrete T cell subpopulations but not for absolute B cell responsiveness. Copyright © 1979 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim