IgM monomers accelerate disease manifestations in autoimmune-prone Fas-deficient mice

• Published in: Journal of autoimmunity Vol. 23; no. 4; pp. 333 - 343
• Main Authors: Youd, Michele E., Luus, Lia, Corley, Ronald B.
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 01.12.2004; Elsevier
• Subjects: Amino Acid Sequence; Animals; Antibodies, Antinuclear - blood; Antibody Formation - physiology; Antigen-Antibody Complex - analysis; Antigen-Antibody Complex - metabolism; Autoimmune Diseases - genetics; Autoimmune Diseases - immunology; Autoimmunity; Autoimmunity - genetics; Autoimmunity - physiology; B lymphocytes; Biological and medical sciences; fas Receptor - genetics; Fundamental and applied biological sciences. Psychology; Fundamental immunology; General aspects; Hypergammaglobulinemia - genetics; Hypergammaglobulinemia - metabolism; IgM; Immunoglobulin G - blood; Immunoglobulin J-Chains - genetics; Immunoglobulin M - genetics; Immunoglobulin M - physiology; Immunopathology; Kidney - immunology; lpr; Lupus; Medical sciences; Mice; Mice, Transgenic; Molecular Sequence Data; Mutation - genetics; Splenomegaly - genetics; Splenomegaly - immunology; Transgenes - genetics; Autoimmunity; Lupus; ANA; B lymphocytes; H; IC; ER; LMW IgM; IgM; lpr; Immunopathology; Connective tissue disease; Skin disease; Rodentia; Autoimmune disease; B-Lymphocyte; Vertebrata; Immunology; Mammalia; Systemic lupus erythematosus; Mouse; Animal; Systemic disease; Fas Antigen; B lymphocytes: IgM; Monomer
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1016/j.jaut.2004.09.001

The monomeric form of IgM, also known as low molecular weight IgM, is found in increased concentrations in patients chronically infected with a variety of viral and bacterial pathogens or suffering from various autoimmune diseases. Whether monomeric IgM contributes to the disease process, however, is not known. To address this question, transgenic mice were created that secreted elevated levels of IgM monomers. In normal mice (C57BL/6), the presence of IgM monomers did not alter the composition of the immune system significantly: lymphocyte subsets and serum antibody levels were normal, with the exception of increased levels of IgM due to the presence of the monomers. Immune responses also appeared to be normal. Transgenic mice did develop antinuclear antibodies (ANA) earlier than non-transgenic littermates, but did not develop further indications of autoimmune disease. When the transgene was expressed in the autoimmune-prone strain of mice, B6.MRL- Tnfrsf6 lpr (B6/lpr), these mice developed autoimmune manifestations more rapidly than non-transgenic littermates, including hypergammaglobulinemia, splenomegaly, and ANA production. Transgenic mice also displayed earlier evidence of immune complex deposition in the kidneys. From these results, we conclude that monomeric IgM does not induce autoimmune disease, but its presence can accelerate the onset of autoimmune manifestations in otherwise autoimmune prone animals.