title: B cell positive selection by soluble self-antigen.
abstract: It is well established that autoreactive B cells undergo negative selection. This stands in paradox with the high frequency of so-called natural autoreactive B cells producing low affinity polyreactive autoantibodies with recurrent specificities, suggesting that these B cells are selected on the basis of their autoreactivity. We previously described two transgenic mouse lines (with and without IgD) producing a human natural autoantibody (nAAb) that binds ssDNA and human Fcgamma. In the absence of human IgG, nAAb-transgenic B cells develop normally. By crossing these mice with animals expressing knockin chimeric IgG with the human Fcgamma, we now show that the constitutive expression of chimeric IgG promotes the increase of nAAb-expressing B cells. This positive selection is critically dependent on the presence of IgD, occurs in the spleen, and concerns all mature B cell subsets, with a relative preferential enrichment of marginal zone B cells. These data support the view that soluble self-Ags can result in positive clonal selection.
authors.affiliation: Laboratoire d'Immunopathologie, Institut d'Hématologie et d'Immunologie, 1 place de l'hôpital, 67091 Strasbourg Cedex, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Julien
authors.forename: Pauline
authors.initials: P
authors.lastname: Soulas
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Garaud
authors.forename: Thierry
authors.initials: T
authors.lastname: Martin
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Pasquali
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000235:genetics; D001324:Autoantigens / Q000096:biosynthesis / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000235:genetics; D018985:Epitopes, B-Lymphocyte / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007072:Immunoglobulin D / Q000096:biosynthesis / Q000235:genetics; D007074:Immunoglobulin G / Q000235:genetics / Q000502:physiology; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000502:physiology; D012995:Solubility; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D018985:Epitopes, B-Lymphocyte; D007072:Immunoglobulin D; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins