Anti-IgD antibody attenuates collagen-induced arthritis by selectively depleting mature B-cells and promoting immune tolerance

• Published in: Journal of autoimmunity Vol. 35; no. 1; pp. 86 - 97
• Main Authors: Nguyen, Tue G, Little, Christopher B, Yenson, Vanessa M, Jackson, Christopher J, McCracken, Sharon A, Warning, Julia, Stevens, Veronica, Gallery, Eileen G, Morris, Jonathan M
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.08.2010; Elsevier
• Subjects: Adaptive; Adaptive Immunity - drug effects; Allergy and Immunology; Animal models; Animals; Antibodies, Anti-Idiotypic - pharmacology; Arthritis; Arthritis, Experimental - drug therapy; Arthritis, Experimental - immunology; Arthritis, Experimental - pathology; Arthritis, Experimental - physiopathology; Autoimmune; B cell; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; B-Lymphocytes - pathology; Biological and medical sciences; Disease Progression; Diseases of the osteoarticular system; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; IgD; Immune Tolerance - drug effects; Immunity, Innate - drug effects; Immunotherapy; Inflammatory joint diseases; Innate; Joints - drug effects; Joints - pathology; Lymphocyte Depletion; Lymphocyte Subsets - drug effects; Lymphocyte Subsets - immunology; Lymphocyte Subsets - metabolism; Lymphocyte Subsets - pathology; Male; Medical sciences; Mice; Mice, Inbred DBA; T helper cell; Th1 Cells - drug effects; Th1 Cells - immunology; Th2 Cells - drug effects; Th2 Cells - immunology; Tolerance; B cell; Adaptive; IgD; Tolerance; Arthritis; Autoimmune; Innate; T helper cell; Autoimmunity; Immunopathology; Animal model; Antibody; Diseases of the osteoarticular system; Autoimmune disease; Helper cell; Inflammatory joint disease; B-Lymphocyte; Chronic; Depletion; Immunology; Rheumatoid arthritis; Immune tolerance; T-Lymphocyte; Collagen induced arthritis
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1016/j.jaut.2010.03.003

Abstract Membrane (m)IgD forms a major part of B-cell receptor complexes. Its wider role in the immune system has been enigmatic. Stimulation of mIgD with an antibody (anti-IgD) can activate B-cells and elicit a broad immune response in vivo . Given the role of B-cells in autoimmune diseases and the profound impact of anti-IgD on B-cells, the potential effects of anti-IgD on autoimmune conditions are intriguing and yet to be explored. Here we report a novel therapeutic effect of anti-IgD in the collagen-induced arthritis (CIA) mouse model. Administration of anti-IgD at the onset of early clinical symptoms as a therapeutic intervention, but not as a prophylactic treatment, significantly ameliorates disease severity and joint pathology. Anti-IgD treatment selectively depletes mature B cells while it spares regulatory B-cell subsets. This results in a significant reduction of autoantibody levels but does not affect antibody responses to a T-cell-dependent antigen. Therapeutic treatment with anti-IgD increases the numbers of regulatory B-cells and regulatory T-cells whilst it augments adaptive Th1/Th2 responses in vivo . In human PBMC samples, anti-IgD also promotes adaptive Th1/Th2 responses and modulates the innate responses toward an anti-inflammatory Th2-biased response. Collectively, anti-IgD treatment may offer a selective approach to B-cell depletion that also promotes immune tolerance and anti-inflammatory tendencies without compromising the general adaptive B-cell and T-cell responses. The multiple mechanisms of action by anti-IgD treatment suggest a wider clinical application for a number of chronic inflammatory and autoimmune conditions.