The Journal of Experimental Medicine
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Published 3 December 2001. doi:10.1084/jem.194.11.1691
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© Rockefeller University Press, 0022-1007/2001/12/1691/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 11, December 3, 2001 1691-1698

Brief Definitive Report

Maturation of Marginal Zone and Follicular B Cells Requires B Cell Activating Factor of the Tumor Necrosis Factor Family and Is Independent of B Cell Maturation Antigen

Pascal Schneider1, Hisakazu Takatsuka1, Anne Wilson3, Fabienne Mackay4, Aubry Tardivel1, Susanne Lens1, Teresa G. Cachero5, Daniela Finke2, Friedrich Beermann2 and Jürg Tschopp1

1 Institute of Biochemistry, BIL Biomedical Research Center, University of Lausanne, the
2 Swiss Institute for Experimental Cancer Research, Lausanne Branch, University of Lausanne, Boveresses 155, CH-1066 Epalinges, Switzerland
3 Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Boveresses 155, CH-1066 Epalinges, Switzerland
4 Garvan Institute of Medical Research, St. Vincent Hospital, Darlinghurst NSW 2010, Sydney, Australia
5 Biogen, Department of Protein Chemistry, Cambridge, MA 02142

Address correspondence to Jürg Tschopp, Institute of Biochemistry, University of Lausanne, Ch. des Boveresses 155, CH-1066 Epalinges, Switzerland. Phone: 41-21-692-5738/5706; Fax: 41-21-692-5705; E-mail: Jurg.Tschopp{at}ib.unil.ch

B cells undergo a complex series of maturation and selection steps in the bone marrow and spleen during differentiation into mature immune effector cells. The tumor necrosis factor (TNF) family member B cell activating factor of the TNF family (BAFF) (BLyS/TALL-1) plays an important role in B cell homeostasis. BAFF and its close homologue a proliferation-inducing ligand (APRIL) have both been shown to interact with at least two receptors, B cell maturation antigen (BCMA) and transmembrane activator and cyclophilin ligand interactor (TACI), however their relative contribution in transducing BAFF signals in vivo remains unclear. To functionally inactivate both BAFF and APRIL, mice transgenic for a soluble form of TACI were generated. They display a developmental block of B cell maturation in the periphery, leading to a severe depletion of marginal zone and follicular B2 B cells, but not of peritoneal B1 B cells. In contrast, mice transgenic for a soluble form of BCMA, which binds APRIL, have no detectable B cell phenotype. This demonstrates a crucial role for BAFF in B cell maturation and strongly suggests that it signals via a BCMA-independent pathway and in an APRIL-dispensable way.

Key Words: TNF • transgene • receptor • ligand • lymphocyte


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