Depression by Fc gamma receptor ligands of SRBC-induced IgM-PFC generation in human blood mononuclear cell cultures.

A tissue-culture system to stimulate human peripheral blood mononuclear cells (PBMC) has been employed in which IgM plaque-forming cell (IgM PFC) generation in response to sheep erythrocytes (SRBC) is dependent on macrophages and T suppressor and helper lymphocytes. In this system PBMC from normal subjects give IgM PFC responses ranging from 26 to 938 PFC/culture. Heat-aggregated human IgG or immune complexes present for the duration of culture induce a significant depression of PFC. Unaggregated IgG has no effect on the response or only a moderate stimulatory effect at the highest dose. The results of these experiments are compatible with previous results in a murine system, which indicated that Fc gamma receptor-positive (Fc gamma R+) cells in the suppressor subset are the target for aggregated IgG and induce depression of the PFC response. A similar mechanism may be operating in the human system described here, although the target cell has not been identified. These results may reflect a mechanism of immunomodulation dependent on interaction of Fc receptor (FcR) ligands with FcR, which may play a role in the pathogenesis of immune complex disorders.