Selective silencing of disease-associated B-lymphocytes by chimeric molecules targeting their Fc IIb receptor

• Published in: International immunology Vol. 20; no. 2; pp. 165 - 175
• Main Authors: Mihaylova, N., Voynova, E., Tchorbanov, A., Nikolova, M., Michova, A., Todorov, T., Srebreva, L., Taskov, H., Vassilev, T.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford Publishing Limited (England) 01-02-2008
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxm133

The presently used approaches to silence autoreactive disease-associated B cells act indiscriminately and more specific therapies are obviously needed. In the present study, we analyze the ability of a chimeric antibody to suppress selectively pathological autoreactive B-lymphocytes in lupus-prone mice by cross-linking their surface Ig receptors with the inhibitory IgG FcγRIIb receptors. The chimera was constructed by coupling an immunodominant mouse Histone 1 peptide to a rat monoclonal anti-mouse CD32 (FcγRIIb) antibody. The administration of these chimeric molecules to MRL/lpr mice with initial and with full-blown disease resulted in the reduction of the levels of IgG anti-Histone 1 antibodies, of the albuminuria levels, of the size of lymphoid organs and in prevention of the development of skin lesions. The observed effect was limited to lupus-associated B cells only, as the treatment did not decrease the IgG antibody response to an administered foreign antigen. This study demonstrates the possibility to silence selectively autoreactive B cells and to delay the progression of an autoimmune disease using chimeric antibody molecules.