title: Marginal zone B cells transport IgG3-immune complexes to splenic follicles.
abstract: Ag administered together with specific IgG3 induces a higher Ab response than Ag administered alone, an effect requiring the presence of complement receptors 1 and 2 (CR1/2). In this study, we have investigated the fate of Ag, the development of germinal centers (GCs), and the Ab response after i.v. administration of IgG3 anti-trinitrophenyl (TNP) in complex with OVA-TNP. After 2 h, OVA-TNP was detected on marginal zone (MZ) B cells, and a substantial amount of Ag was detected in splenic follicles and colocalized with follicular dendritic cells (FDCs). After 10 d, the percentage of GCs and the IgG responses were markedly higher than in mice immunized with uncomplexed OVA-TNP. The effects of IgG3 were dependent on CR1/2 known to be expressed on B cells and FDCs. Using bone marrow chimeric mice, we demonstrate that an optimal response to IgG3-Ag complexes requires that CR1/2 is expressed on both cell types. These data suggest that CR1/2(+) MZ B cells transport IgG3-Ag-C complexes from the MZ to the follicles, where they are captured by FDCs and induce GCs and IgG production. This pathway for initiating the transport of Ags into splenic follicles complements previously known B-cell dependent pathways where Ag is transported by 1) MZ B cells, binding large Ags-IgM-C complexes via CR1/2; 2) recirculating B cells, binding Ag via BCR; or 3) recirculating B cells, binding IgE-Ag complexes via the low-affinity receptor for IgE, CD23.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, SE-75123, Uppsala, Sweden.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, SE-75123, Uppsala, Sweden.
authors.forename: Zhoujie
authors.initials: Z
authors.lastname: Ding
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, SE-75123, Uppsala, Sweden.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, SE-75123, Uppsala, Sweden birgitta.heyman@imbim.uu.se.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Heyman
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D020566:Dendritic Cells, Follicular / Q000276:immunology*; D005260:Female; D000068876:Fingolimod Hydrochloride; D018858:Germinal Center / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D011409:Propylene Glycols / Q000494:pharmacology; D017464:Receptors, Complement 3d / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D014301:Trinitrobenzenes / Q000276:immunology
chemical_list: D000936:Antigen-Antibody Complex; D000941:Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D017464:Receptors, Complement 3d; D014301:Trinitrobenzenes; D007073:Immunoglobulin E; D010047:Ovalbumin; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine