title: B-cell inhibition by cross-linking CD79b is superior to B-cell depletion with anti-CD20 antibodies in treating murine collagen-induced arthritis.
abstract: Depletion of B cells with the anti-CD20 antibody rituximab is an established therapy for rheumatoid arthritis. However, rituximab has only moderate efficacy, most likely due to insufficient depletion of B cells in lymphoid organs and expansion of pathogenic B cells. We found that an antibody against mouse CD79b profoundly blocks B-cell proliferation induced via the B-cell receptor, CD40, CD180, and chondroitin sulfate, but not via TLR4 or TLR9. Treatment with anti-CD79b also induces death in resting and activated B cells. B-cell inhibition is mediated by cross-linkage of CD79b, but independent of Fc-receptor engagement. In the model of collagen-induced arthritis, an antibody against mouse CD20 depletes B cells very efficiently but fails to suppress the humoral immune response against collagen and the development of arthritis. In contrast, the antibody against CD79b, and a deglycosylated variant of this antibody, almost completely inhibits the increase in anti-collagen antibodies and the development of arthritis. In mice with established arthritis only the fully glycosylated antibody against CD79b is effective. Our data show that targeting B cells via CD79b is much more effective than B-cell depletion with anti-CD20 antibodies for therapy of arthritis. These findings may have important implications for treatment of B-cell-mediated autoimmune diseases.
authors.affiliation: Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Hilke
authors.initials: H
authors.lastname: Brühl
authors.forename: Josef
authors.initials: J
authors.lastname: Cihak
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Talke
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodriguez Gomez
authors.forename: Fabian
authors.initials: F
authors.lastname: Hermann
authors.forename: Nicole
authors.initials: N
authors.lastname: Goebel
authors.forename: Kerstin
authors.initials: K
authors.lastname: Renner
authors.forename: Jiří
authors.initials: J
authors.lastname: Plachý
authors.forename: Manfred
authors.initials: M
authors.lastname: Stangassinger
authors.forename: Susanne
authors.initials: S
authors.lastname: Aschermann
authors.forename: Falk
authors.initials: F
authors.lastname: Nimmerjahn
authors.forename: Matthias
authors.initials: M
authors.lastname: Mack
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D019013:CD40 Antigens / Q000276:immunology; D051925:CD79 Antigens / Q000037:antagonists & inhibitors* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D007152:Immunologic Capping / Q000187:drug effects; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD; D018501:Antirheumatic Agents; D019013:CD40 Antigens; D051925:CD79 Antigens; C497884:Cd79b protein, mouse; C490500:Ly78 protein, mouse; D011947:Receptors, Antigen, B-Cell; D000069283:Rituximab
keywords: Arthritis; B-cell depletion; B-cell inhibition; B cells; CD79b; Humoral immune response