Surface Immunog lobu l in Receptors BY KENNETH L . ROCK , BARUJ BENACERRAF , AND ABUL

Cells of the monocyte/macrophage lineage, dendritic cells, and a variety of other cell types that express class II histocompatibility (Ia) molecules on their surfaces are capable of presenting foreign protein antigens to and stimulating Iarestricted inducer (helper) T lymphocytes (1-3). After the demonstration that B cells also bear Ia antigens (4) and that at least some interactions between antigenspecific helper T cells and B lymphocytes are Ia restricted (5), many investigators have attempted to determine whether B lymphocytes can also function as antigenpresenting cells. Among the earliest studies to demonstrate that B cells can, in fact, present antigens to T cells were the experiments showing that macrophagedepleted murine B cells incubated with protein antigens could stimulate immune T lymphocytes to proliferate in an Ia-restricted fashion (3). More convincing evidence for the role of B cells in presenting antigen came from studies of Chesnut and Grey (6), who showed that macrophage-depleted splenocytes cultured with rabbit anti-mouse immunoglobulin (Ig), but not rabbit IgG lacking anti-Ig activity, could stimulate rabbit 3,-globulin-primed T cells to proliferate in vitro (6). This result not only established the ability of B lymphocytes to present protein antigens to T cells but also indicated that their surface Ig receptors played an important role in this phenomenon. Subsequently, it has been shown that resting and mitogen-activated normal B lymphocytes as well as a variety of Ia-positive B cell-derived tumors and cell lines are capable of presenting foreign proteins to Ia-restricted, antigen-reactive T lymphocytes (7-12). In all these situations, high concentrations of antigens are required and surface Ig receptors play no role. In fact, the amounts of antigens required for such presentation are comparable to those observed with other accessory cells (1, 2), but in vast excess of the concentrations required for T cell-dependent, antigen-specific, major histocompatibility-restricted activation of primed B lymphocytes (13). Thus, although cloned B cell tumors and normal B lymphocytes are valuable for analyzing the cellular and molecular events in antigen presentation (e.g., 14, 15), the relevance of such studies to physiologic antigen-specific T-B interactions involving cognate recognition of linked antigenic determinants is unclear. In an attempt to develop systems for analyzing the interactions between antigen-specific T and B lymphocytes, we have investigated the ability of B cells