TACI-Ig Neutralizes Molecules Critical for B Cell Development and Autoimmune Disease: Impaired B Cell Maturation in Mice Lacking BLyS

• Published in: Immunity (Cambridge, Mass.) Vol. 15; no. 2; pp. 289 - 302
• Main Authors: Gross, Jane A, Dillon, Stacey R, Mudri, Sherri, Johnston, Janet, Littau, Alisa, Roque, Richard, Rixon, Mark, Schou, Ole, Foley, Kevin P, Haugen, Harald, McMillen, Susan, Waggie, Kim, Schreckhise, Randy W, Shoemaker, Kim, Vu, Tuyen, Moore, Margaret, Grossman, Angelika, Clegg, Chris H
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-08-2001
• Subjects: Animals; Antibody Formation; APRIL protein; Arthritis, Rheumatoid - etiology; Arthritis, Rheumatoid - immunology; Autoantibodies - blood; Autoimmune Diseases - etiology; B-Cell Activation Factor Receptor; B-Lymphocytes - classification; B-Lymphocytes - immunology; BLyS protein; Cell Differentiation; Cell Lineage; Collagen - immunology; Homozygote; Immunoglobulins - blood; Membrane Proteins; Mice; Mice, Transgenic; Phenotype; Receptors, Tumor Necrosis Factor - genetics; Receptors, Tumor Necrosis Factor - immunology; Receptors, Tumor Necrosis Factor - metabolism; Transmembrane Activator and CAML Interactor Protein; tumor necrosis factor receptors
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/S1074-7613(01)00183-2

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.