B cell positive selection by soluble self-antigen.
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.
Julien
Sylvie
S
Laboratoire d'Immunopathologie, Institut d'Hématologie et d'Immunologie, 1 place de l'hôpital, 67091 Strasbourg Cedex, France.
Soulas
Pauline
P
Garaud
Jean-Claude
JC
Martin
Thierry
T
Pasquali
Jean-Louis
JL
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
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