LOCAL SYNTHESIS OF C3 WITHIN THE SPLENIC LYMPHOID COMPARTMENT CAN RECONSTITUTE THE IMPAIRED IMMUNE-RESPONSE IN C3-DEFICIENT MICE

Mice bearing a disrupted C3 locus (C3(-/-)) have an impaired Ab respon se to T-dependent Ags (bacteriophage phi X 174 and nuclear protein-key hole limpet hemocyanin) characterized by a reduction in number and siz e of germinal centers and impaired retention of Ag by follicular dendr itic cells, To test the importance of C3 synthesized locally within th e lymphoid compartment during an immune response to T-dependent Ag, we reconstituted C3(-/-) mice with wild-type bone marrow of MHC-identica l littermates. Engraftment not only restored local C3 synthesis in the spleen, but also rescued the impaired humoral response. The major sou rce of C3 mRNA was MOMA-2(+) macrophages localized within the white pu lp areas of the spleen, Interestingly, C3 expression is apparently reg ulated as C3 mRNA was not detected in splenic sections of nonimmune mi ce, Furthermore, local C3 synthesis by donor macrophages reversed the impaired Ag trapping by splenic follicular dendritic cells in C3-defic ient mice.