Abrogation of pathogenic IgG autoantibody production in CD40L gene-deleted lupus-prone New Zealand Black mice

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2011-05, Vol.139 (2), p.215-227
• Main Authors: Pau, Evelyn, Chang, Nan-Hua, Loh, Christina, Lajoie, Ginette, Wither, Joan E
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; Antibody Formation - physiology; Antigens, CD - metabolism; Autoantibodies - biosynthesis; Autoantibodies - blood; Autoantibodies - immunology; Autoantigens - immunology; B cells; B-Cell Activating Factor - genetics; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - metabolism; B-Lymphocyte Subsets - pathology; Biological and medical sciences; Bone Marrow Cells - immunology; Bone Marrow Cells - metabolism; Bone Marrow Cells - pathology; CD40 Ligand - genetics; CD40 Ligand - metabolism; CD40–CD40L; Cell Proliferation - drug effects; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - pathology; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression - genetics; Gene Expression - immunology; Immunoglobulin A - blood; Immunoglobulin A - immunology; Immunoglobulin Class Switching - physiology; Immunoglobulin G - biosynthesis; Immunoglobulin G - blood; Immunoglobulin G - immunology; Immunoglobulin M - blood; Immunoglobulin M - immunology; Immunophenotyping; Interferon Type I - genetics; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - metabolism; Lupus Erythematosus, Systemic - pathology; Lupus Nephritis - immunology; Lupus Nephritis - metabolism; Lupus Nephritis - pathology; Lymphocyte Activation - drug effects; Lymphocyte Activation - physiology; Macrophages - immunology; Macrophages - metabolism; Macrophages - pathology; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Inbred NZB; Mice, Knockout; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Spleen - immunology; Spleen - metabolism; Spleen - pathology; Systemic lupus erythematosus; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - pathology; Toll-Like Receptors - agonists; Tumor Necrosis Factor-alpha - genetics
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2011.02.005

Abstract New Zealand Black (NZB) mice spontaneously develop a lupus-like autoimmune disease. Since CD40–CD40L interactions are important for B cell class-switch recombination and germinal center formation, we sought to understand the impact of these interactions on the immune abnormalities in NZB CD40L gene-deleted (CD40L−/− ) mice in vivo . NZB.CD40L−/− mice demonstrated abrogation of all IgG autoantibodies tested and attenuated kidney disease. However, polyclonal B cell activation in vivo and B cell proliferation and class-switching in response to TLR ligands in vitro were preserved in the absence of CD40L in NZB mice. Although, plasmacytoid dendritic cell expansion and elevated BAFF production were unaffected by the absence of CD40L, there was some evidence that IFN-α-induced gene expression was reduced in the bone marrow of NZB.CD40L−/− mice. Our results suggest that CD40–CD40L interactions play an important role in promoting pathogenic IgG autoantibody production and kidney disease in NZB mice.