title: IgG2a-mediated enhancement of antibody responses is dependent on FcRgamma+ bone marrow-derived cells.
abstract: 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 IgG1 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 FcgammaRI, FcgammaRIII and FcepsilonRI owing to gene targeting of the common FcRgamma subunit (FcRgamma-/-). Here we show that enhancement after immunization with BSA-TNP/IgG2a complexes is restored in irradiated FcRgamma-/- recipients transferred with wild-type (FcRgamma+/+) bone marrow (BM) cells. In contrast, no enhancement is seen in FcRgamma+/+ irradiated animals reconstituted with FcRgamma-/- BM cells. We conclude that IgG2a-mediated enhancement of Ab responses is dependent on the presence of FcgammaRI and/or FcgammaRIII on BM-derived cells and that the presence of these receptors on the radioresistant follicular dendritic cell is not essential.
authors.affiliation: Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Dag Hammerskjölds väg 20, SE-751 85 Uppsala, Sweden. Teresita.Diaz_de_Stahl@genpat.uu.se
authors.forename: T
authors.initials: T
authors.lastname: Diaz de Ståhl
authors.forename: B
authors.initials: B
authors.lastname: Heyman
mesh_terms: D000818:Animals; D000917:Antibody Formation; D000936:Antigen-Antibody Complex / Q000008:administration & dosage; D001854:Bone Marrow Cells / Q000276:immunology*; D002417:Cattle; D002678:Chimera / Q000276:immunology; D007114:Immunization; D007074:Immunoglobulin G / Q000008:administration & dosage*; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008819:Mice, Nude; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D017452:Receptors, IgG; C038601:trinitrophenyl-bovine serum albumin; D012710:Serum Albumin, Bovine