Immunity
Volume 15, Issue 2, August 2001, Pages 289-302
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Article
TACI-Ig Neutralizes Molecules Critical for B Cell Development and Autoimmune Disease: Impaired B Cell Maturation in Mice Lacking BLyS

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Abstract

BLyS and APRIL have similar but distinct biological roles, mediated through two known TNF receptor family members, TACI and BCMA. We show that mice treated with TACI-Ig and TACI-Ig transgenic mice have fewer transitional T2 and mature B cells and reduced levels of circulating immunoglobulin. TACI-Ig treatment inhibits both the production of collagen-specific Abs and the progression of disease in a mouse model of rheumatoid arthritis. In BLyS-deficient mice, B cell development is blocked at the transitional T1 stage such that virtually no mature B cells are present, while B-1 cell numbers are relatively normal. These findings further elucidate the roles of BLyS and APRIL in modulating B cell development and suggest that BLyS is required for the development of most but not all mature B cell populations found in the periphery.

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Present address: Millennium Pharmaceuticals, Inc., 75 Sidney Street, Cambridge, Massachusetts 02139.