IgG2a-mediated enhancement of antibody responses is dependent on FcR gamma(+) bone marrow-derived cells

Antibodies (Ab) administered in complex with antigens (Ag) have the capacit y 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 a nd IgG2a BSA-specific Ab response compared to immunization with the Ag alon e. Enhancement was absent in nude mice, demonstrating the requirement of T cells for this regulation. Secondary immunization with BSA alone in mice pr eviously primed with BSA-TNP/IgG2a led to a dramatic increase of Ab product ion, 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 comple xes is restored in irradiated FcR gamma (-/-) recipients transferred with w ild-type (FcR gamma (+/+)) bone marrow (BM) cells. In contrast, no enhancem ent is seen in FcR gamma (+/+) irradiated animals reconstituted with FcR ga mma (-/-) BM cells. We conclude that IgG2a-mediated enhancement of Ab respo nses 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 radioresista nt follicular dendritic cell is not essential.