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B cell-activating factor belonging to the TNF family acts through separate receptors to support B cell survival and T cell-independent antibody formation

Abstract

The TNF-related ligand, B cell-activating factor belonging to the TNF family (BAFF), is necessary for normal B cell development and survival, and specifically binds the receptors transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), B cell maturation Ag (BCMA), and BAFF-R. Similarities between mice completely lacking BAFF and A/WySnJ strain mice that express a naturally occurring mutant form of BAFF-R suggest that BAFF acts primarily through BAFF-R. However, the nearly full-length BAFF-R protein expressed by A/WySnJ mice makes unambiguous interpretation of receptor function in these animals impossible. Using homologous recombination we created mice completely lacking BAFF-R and compared them directly to A/WySnJ mice and to mice lacking BAFF. BAFF-R-null mice exhibit loss of mature B cells similar to that observed in BAFF(-/-) and A/WySnJ mice. Also, mice lacking both TACI and BCMA simultaneously exhibit no B cell loss, thus confirming that BAFF-R is the primary receptor for transmitting the BAFF-dependent B cell survival signal. However, while BAFF-R-null mice cannot carry out T cell-dependent Ab formation, they differ from BAFF-deficient mice in generating normal levels of Ab to at least some T cell-independent Ags. These studies clearly demonstrate that BAFF regulates Ab responses in vivo through receptors in addition to BAFF-R.

Type Journal
ISBN 0022-1767 (Print)
Authors Shulga-Morskaya, S.;Dobles, M.;Walsh, M. E.;Ng, L. G.;MacKay, F.;Rao, S. P.;Kalled, S. L.;Scott, M. L. :
Publisher Name JOURNAL OF IMMUNOLOGY
Published Date 2004-01-01
Published Volume 173
Published Issue 4
Published Pages 2331-41
Status Published in-print
URL link to publisher's version http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15294946
OpenAccess link to author's accepted manuscript version https://publications.gimr.garvan.org.au/open-access/1848