Anti-IgD antibody attenuates collagen-induced arthritis by selectively depleting mature B-cells and promoting immune tolerance.
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.
Nguyen
Tue G
TG
Perinatal Research, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia. tgnguyen@med.usyd.edu.au <tgnguyen@med.usyd.edu.au>
Little
Christopher B
CB
Yenson
Vanessa M
VM
Jackson
Christopher J
CJ
McCracken
Sharon A
SA
Warning
Julia
J
Stevens
Veronica
V
Gallery
Eileen G
EG
Morris
Jonathan M
JM
D056704:Adaptive Immunity / Q000187:drug effects; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D007167:Immunotherapy; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008212:Lymphocyte Depletion; D016131:Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; C039951:anti-IgD