TACI-Ig neutralizes molecules critical for B cell development and autoimmune disease. impaired B cell maturation in mice lacking BLyS.
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.
Gross
J A
JA
Department of Immunology, 1201 Eastlake Avenue East, Seattle, WA 98102, USA. grossj@zgi.com
Dillon
S R
SR
Mudri
S
S
Johnston
J
J
Littau
A
A
Roque
R
R
Rixon
M
M
Schou
O
O
Foley
K P
KP
Haugen
H
H
McMillen
S
S
Waggie
K
K
Schreckhise
R W
RW
Shoemaker
K
K
Vu
T
T
Moore
M
M
Grossman
A
A
Clegg
C H
CH
D000818:Animals; D000917:Antibody Formation; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000209:etiology*; D053265:B-Cell Activation Factor Receptor; D001402:B-Lymphocytes / Q000145:classification / Q000276:immunology*; D002454:Cell Differentiation; D019070:Cell Lineage; D003094:Collagen / Q000276:immunology; D006720:Homozygote; D007136:Immunoglobulins / Q000097:blood; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053303:Transmembrane Activator and CAML Interactor Protein
D001323:Autoantibodies; D053265:B-Cell Activation Factor Receptor; C120197:BLyS receptor; D007136:Immunoglobulins; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; C486361:Tnfrsf13b protein, mouse; C486662:Tnfrsf13c protein, mouse; D053303:Transmembrane Activator and CAML Interactor Protein; D003094:Collagen