B Lymphocyte‐Antigen Interactions in the Initiation of Tolerance or Immunity

The dilemma in whicli we find ourselves iii relation to mechanisms of B cell activation illustrates well the limitations of the reductionist approach of conventional laboratory science (Bumet 1969). Any reasonably satisfying intellectual picture needs to encompass at least three problem streams: the entry, transport, trapping, retention and catabolism of antigen (Nossal & Ada 1971); the collaborative phenomena involving T cells, macrophages and B cells which are frequently required for activation (Miller 1972); and the elaborate events of B cell proliferation and differentiation underlying antibody production, immunological memory, germinal centre formation and affinity maturation (Siskind et al. 1966). Furthermore, as we hope to show, activation ciinnot be understood without paying heed to the opposite option confronting the lymphocyte, namely tolerance, and this in turn needs to be seen in the context of B lymphocyte ontogeny (Nossal & Pike 1973, 1975). Nevertheless, and for good reason, most of the debate in the recent literature on B cell activation has focussed on an extremely limited segment of this spectrum, namely the induction of mitogenesis or IgM antibody synthesis in short-term tissue cultures. In fact, it is becoming increasingly fashionable to restrict attention to molecular events occurring during the first minutes or hours of activation. The attractions of the simplified model systems are obvious, and the present paper will refer frequently to them.