title: Transgenic B lymphocytes expressing a human cold agglutinin escape tolerance following experimental infection of mice by Mycoplasma pulmonis.
abstract: Several microbial infections, including Mycoplasma pneumoniae respiratory infection, are capable, in man, of transiently inducing the expression of anti-red blood cell autoantibody called cold agglutinins (CA). To analyze the mechanisms by which immune tolerance is broken following a mycoplasma infection, we used transgenic mice expressing a pathogenic human CA, designated CA-GAS, specific for sialylated carbohydrates. In these mice peripheral deletion of autoreactive B lymphocytes and receptor editing, prevent the development of autoimmune hemolytic anemia. Experimental infections of transgenic mice with Mycoplasma pulmonis resulted in a high anti-mycoplasma antibody response (despite a severe B cell depletion at the onset of infection), and an important induction of serum CA concentrations, reaching in some mice pathological titers. Whereas in naïve mice, only a small percentage of CA-expressing cells could be detected, in infected mice, a majority of circulating B lymphocytes were large B220(-) cells, which expressed the transgenic immunoglobulin. Immunization of the transgenic mice with keyhole limpet hemocyanin and Freund's adjuvant, to nonspecifically stimulate the expression of the passenger transgenes, only moderately increased the CA titers. These results indicate that M. pulmonis infection is capable of breaking immune tolerance in the CA-transgenic mice, in part through specific activation of CA-expressing B lymphocytes. This experimental infection mimics the induction of CA in humans and provide an animal model for studying the genesis of the autoimmune hemolytic anemia.
authors.affiliation: Unité d'Immuno-Hémathologie et d'Immunopathologie, Institut Pasteur, Paris, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Havouis
authors.forename: Gérard
authors.initials: G
authors.lastname: Dumas
authors.forename: Isabelle
authors.initials: I
authors.lastname: Chambaud
authors.forename: Patrick
authors.initials: P
authors.lastname: Ave
authors.forename: Michel
authors.initials: M
authors.lastname: Huerre
authors.forename: Alain
authors.initials: A
authors.lastname: Blanchard
authors.forename: Guillaume
authors.initials: G
authors.lastname: Dighiero
authors.forename: Christine
authors.initials: C
authors.lastname: Pourcel
mesh_terms: D000373:Agglutinins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D000744:Anemia, Hemolytic, Autoimmune / Q000209:etiology* / Q000276:immunology; D000818:Animals; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex / Q000276:immunology; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology; D003450:Cryoglobulins; D004910:Erythrocyte Membrane / Q000276:immunology*; D005620:Freund's Adjuvant; D005803:Genes, Immunoglobulin; D006386:Hemagglutination Tests; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007113:Immunity, Innate; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000276:immunology; D007148:Immunoglobulin mu-Chains / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D009175:Mycoplasma Infections / Q000150:complications / Q000276:immunology*; D019158:N-Acetylneuraminic Acid / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000276:immunology; D017634:Self Tolerance; D019076:Transgenes
chemical_list: D000373:Agglutinins; D000936:Antigen-Antibody Complex; D003450:Cryoglobulins; D007145:Immunoglobulin kappa-Chains; D007148:Immunoglobulin mu-Chains; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; C029443:cold agglutinins; D005620:Freund's Adjuvant; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; D019158:N-Acetylneuraminic Acid