B Cell-Activating Factor Belonging to the TNF Family Acts through Separate Receptors to Support B Cell Survival and T Cell-Independent Antibody Formation
Open Access
- 15 August 2004
- journal article
- research article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 173 (4), 2331-2341
- https://doi.org/10.4049/jimmunol.173.4.2331
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.Keywords
This publication has 46 references indexed in Scilit:
- BCMA Is Essential for the Survival of Long-lived Bone Marrow Plasma CellsThe Journal of Experimental Medicine, 2004
- BAFF/BLyS Receptor 3 Binds the B Cell Survival Factor BAFF Ligand through a Discrete Surface Loop and Promotes Processing of NF-κB2Immunity, 2002
- Blood Dendritic Cells Interact with Splenic Marginal Zone B Cells to Initiate T-Independent Immune ResponsesImmunity, 2002
- DCs induce CD40-independent immunoglobulin class switching through BLyS and APRILNature Immunology, 2002
- BAFF is a survival and maturation factor for mouse B cellsEuropean Journal of Immunology, 2002
- BAFF-R, a Newly Identified TNF Receptor That Specifically Interacts with BAFFScience, 2001
- An Essential Role for BAFF in the Normal Development of B Cells Through a BCMA-Independent PathwayScience, 2001
- TACI-Ig Neutralizes Molecules Critical for B Cell Development and Autoimmune DiseaseImmunity, 2001
- Baff Binds to the Tumor Necrosis Factor Receptor–Like Molecule B Cell Maturation Antigen and Is Important for Maintaining the Peripheral B Cell PopulationThe Journal of Experimental Medicine, 2000
- Different macrophage populations distinguished by means of fluorescent polysaccharides. Recognition and properties of marginal‐zone macrophagesEuropean Journal of Immunology, 1981