Regulation of the T-independent humoral response by TACI.

G U von Bülow, J M van Deursen, R J Bram

Department of Pediatric and Adolescent Medicine and, Mayo Foundation, Rochester, MN 55905, USA.

Immunity 2001 May

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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.