IgG2a-mediated enhancement of antibody responses is dependent on FcRγ+ bone marrow-derived cells

Antibodies (Ab) administered in complex with antigens (Ag) have the capacity to regulate the out-coming specific immune response. Primary immunization with complexes of bovine serum albumin-2,4,6-trinitrophenyl (BSA-TNP) and immunoglobulin (Ig)G2a anti-TNP induced a significant enhancement of IgGl and IgG2a BSA-specific Ab response compared to immunization with the Ag alone. Enhancement was absent in nude mice, demonstrating the requirement of T cells for this regulation. Secondary immunization with BSA alone in mice previously primed with BSA-TNP/IgG2a led to a dramatic increase of Ab production, showing that immune complexes are efficient inducers of immunological memory. IgG-mediated enhancement of Ab responses has previously been shown to be impaired in mice lacking Fc gamma RI, Fc gamma RIII and Fc epsilon RI owing to gene targeting of the common FcR gamma subunit (FcR gamma (-/-)). Here we show that enhancement after immunization with BSA-TNP/IgG2a complexes is restored in irradiated FcR gamma (-/-) recipients transferred with wild-type (FcR gamma (+/+)) bone marrow (BM) cells. In contrast, no enhancement is seen in FcR gamma (+/+) irradiated animals reconstituted with FcR gamma (-/-) BM cells. We conclude that IgG2a-mediated enhancement of Ab responses is dependent on the presence of Fc gamma RI and/or Fc gamma RIII on BM-derived cells and that the presence of these receptors on the radioresistant follicular dendritic cell is not essential.