B-cell inhibition by cross-linking CD79b is superior to B-cell depletion with anti-CD20 antibodies in treating murine collagen-induced arthritis

0442392 - ÚMG 2015 RIV DE eng J - Článek v odborném periodiku
Bruhl, H. - Cihak, J. - Talke, Y. - Rodriguez-Gomez, M. - Hermann, F. - Goebel, N. - Renner, K. - Plachý, Jiří - Stangassinger, M. - Archemann, S. - Nimmerjahn, F. - Mack, M.
B-cell inhibition by cross-linking CD79b is superior to B-cell depletion with anti-CD20 antibodies in treating murine collagen-induced arthritis.
European Journal of Immunology. Roč. 45, č. 3 (2015), s. 705-715. ISSN 0014-2980. E-ISSN 1521-4141
Institucionální podpora: RVO:68378050
Klíčová slova: Arthritis * B cells * B-cell depletion * B-cell inhibition * CD79b * Humoral immune response
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 4.179, rok: 2015

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.
Trvalý link: http://hdl.handle.net/11104/0245232