B Cell-Activating Factor Belonging to the TNF Family Acts through Separate Receptors to Support B Cell Survival and T Cell-Independent Antibody Formation

• Published in: The Journal of immunology (1950) Vol. 173; no. 4; pp. 2331 - 2341
• Main Authors: Shulga-Morskaya, Svetlana, Dobles, Max, Walsh, Meghan E, Ng, Lai Guan, MacKay, Fabienne, Rao, Sambasiva P, Kalled, Susan L, Scott, Martin L
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.08.2004
• Subjects: Animals; Antibody Formation - immunology; B-Cell Activating Factor; B-Cell Activation Factor Receptor; B-Cell Maturation Antigen; B-Lymphocytes - immunology; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Immunohistochemistry; Membrane Proteins - genetics; Membrane Proteins - immunology; Mice; Mice, Mutant Strains; Receptors, Tumor Necrosis Factor - genetics; Receptors, Tumor Necrosis Factor - immunology; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes - immunology; Transmembrane Activator and CAML Interactor Protein; Tumor Necrosis Factor-alpha - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.173.4.2331

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.