Myeloid C3 determines induction of humoral responses to peripheral herpes simplex virus infection

The complement system, in addition to its role in innate immunity, is an important regulator of the B cell response. Complement exists predominantly in the circulation and although the primary source is hepatic, multiple additional cellular sources have been described that can contribute substantially to the complement pool. To date, however, complement produced by these secondary sources has been deemed redundant to that secreted by the liver. In contrast, using a bone marrow chimeric model, we observed that C3 synthesis by myeloid cells, a relatively minor source of complement, provided a critical function during the induction of humoral responses to peripheral HSV infection. Anti-viral Ab, as generated in an efficient humoral response, has been associated with protection from severe consequences of HSV dissemination. This report offers insight into the generation of the adaptive immune response in the periphery and describes a unique role for a nonhepatic complement source.