Regulation of the T-independent humoral response by TACI.
TACI is a TNFR homolog expressed by mature B lymphocytes that has been implicated in the positive regulation of B cell growth and antibody production, as well as in the development of autoimmune disease. Its biology is complex due to the existence of two ligands, BLyS and APRIL, and a homologous receptor, BCMA, that similarly binds both ligands. To determine its critical biological role, we generated TACI knockout mice. Surprisingly, these mice demonstrated a 2-fold increase in numbers of circulating and splenic B cells, apparently due to increased proliferation rate. Maturation of B cells and T-dependent antibody production was normal, but responses to T-independent type II antigens were almost completely abolished. It appears that TACI provides an essential costimulatory signal for the T-independent humoral response.
von Bülow
G U
GU
Department of Pediatric and Adolescent Medicine and, Mayo Foundation, Rochester, MN 55905, USA.
van Deursen
J M
JM
Bram
R J
RJ
D000818:Animals; D000917:Antibody Formation; D053264:B-Cell Activating Factor; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002455:Cell Division; D018390:Gene Targeting; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D018655:Lymphocyte Count; D008565:Membrane Proteins / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D013154:Spleen / Q000002:abnormalities / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D053303:Transmembrane Activator and CAML Interactor Protein; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology
D053264:B-Cell Activating Factor; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; C108467:TNFRSF13B protein, human; C505719:TNFSF13B protein, human; C486361:Tnfrsf13b protein, mouse; C505720:Tnfsf13b protein, mouse; D053303:Transmembrane Activator and CAML Interactor Protein; D014409:Tumor Necrosis Factor-alpha