The role of cell division in the induction of clonal anergy.

The interaction of antigen with lymphocyte antigen receptors can result in either clonal expansion or unresponsiveness (anergy). In 1970, Bretscher and Cohn proposed a two-signal model of lymphocyte activation to explain this paradox: antigen receptor occupancy alone could induce unresponsiveness whereas antigen receptor occupancy plus a costimulatory signal could induce immunity. Here, Marc Jenkins reviews in vitro and in vivo manifestations of clonal anergy and evaluates the ability of the two-signal model to explain these phenomena.