title: Development of self-reactive germinal center B cells and plasma cells in autoimmune Fc gammaRIIB-deficient mice.
abstract: Abnormalities in expression levels of the IgG inhibitory Fc gamma receptor IIB (FcγRIIB) are associated with the development of immunoglobulin (Ig) G serum autoantibodies and systemic autoimmunity in mice and humans. We used Ig gene cloning from single isolated B cells to examine the checkpoints that regulate development of autoreactive germinal center (GC) B cells and plasma cells in FcγRIIB-deficient mice. We found that loss of FcγRIIB was associated with an increase in poly- and autoreactive IgG(+) GC B cells, including hallmark anti-nuclear antibody-expressing cells that possess characteristic Ig gene features and cells producing kidney-reactive autoantibodies. In the absence of FcγRIIB, autoreactive B cells actively participated in GC reactions and somatic mutations contributed to the generation of highly autoreactive IgG antibodies. In contrast, the frequency of autoreactive IgG(+) B cells was much lower in spleen and bone marrow plasma cells, suggesting the existence of an FcγRIIB-independent checkpoint for autoreactivity between the GC and the plasma cell compartment.
authors.affiliation: Max Planck Molecular Immunology Research Group, Max Planck Institute for Infection Biology, 10117 Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tiller
authors.forename: Juliane
authors.initials: J
authors.lastname: Kofer
authors.forename: Cornelia
authors.initials: C
authors.lastname: Kreschel
authors.forename: Christian E
authors.initials: CE
authors.lastname: Busse
authors.forename: Stefan
authors.initials: S
authors.lastname: Riebel
authors.forename: Susanne
authors.initials: S
authors.lastname: Wickert
authors.forename: Felix
authors.initials: F
authors.lastname: Oden
authors.forename: Maria M M
authors.initials: MM
authors.lastname: Mertes
authors.forename: Marc
authors.initials: M
authors.lastname: Ehlers
authors.forename: Hedda
authors.initials: H
authors.lastname: Wardemann
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis; D001323:Autoantibodies / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000502:physiology*; D022801:Complementarity Determining Regions; D018858:Germinal Center / Q000276:immunology*; D007074:Immunoglobulin G / Q000032:analysis; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry; D007668:Kidney / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009707:Nucleosomes / Q000276:immunology; D010950:Plasma Cells / Q000502:physiology*; D017452:Receptors, IgG / Q000172:deficiency / Q000502:physiology*; D027041:Somatic Hypermutation, Immunoglobulin
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D022801:Complementarity Determining Regions; C080571:Fc gamma receptor IIB; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D009707:Nucleosomes; D017452:Receptors, IgG