BAFF receptor explained

BAFF receptor (B-cell activating factor receptor, BAFF-R), also known as tumor necrosis factor receptor superfamily member 13C (TNFRSF13C) and BLyS receptor 3 (BR3), is a membrane protein of the TNF receptor superfamily which recognizes BAFF, an essential factor for B cell maturation and survival.^{[1] [2]} In humans it is encoded by the TNFRSF13C gene.^[3]

Function

B-cell activating factor (BAFF) enhances B-cell survival in vitro and is a regulator of the peripheral B-cell population. The protein encoded by this gene is a receptor for BAFF and is a type III transmembrane protein containing a single extracellular phenylalanine-rich domain. It is thought that this receptor is the principal receptor required for BAFF-mediated mature B-cell survival.^[3] In B cell maturation, due to regulation by BAFF-R, only a limited amount of B-cell will survive.^[4]

Clinical significance

Overexpression of BAFF in mice results in mature B-cell hyperplasia and symptoms of systemic lupus erythematosus (SLE). Also, some SLE patients have increased levels of BAFF in serum. Therefore, it has been proposed that abnormally high levels of BAFF may contribute to the pathogenesis of autoimmune diseases by enhancing the survival of autoreactive B cells, which are cells that show immune response to normal body cells.^[3] Autoreactive B cells are less sensitive toward BAFF and are usually outcompeted by the normal B cells in the maturation process regulated by low BAFF-R expression. An elevated level of BAFF-R can therefore overcome this decreased response and result in accumulation of autoreactive B cells.

BAFF and BAFF-R pair can also down-regulate the cell apoptosis process.^[5]

See also

• B-cell activating factor
• B-cell maturation antigen

References

Further reading

• Laâbi Y, Egle A, Strasser A . TNF cytokine family: more BAFF-ling complexities . Current Biology . 11 . 24 . R1013-6 . December 2001 . 11747837 . 10.1016/S0960-9822(01)00613-3 . 17001236 . free . 2001CBio...11R1013L .
• Book: Defrance T, Casamayor-Pallejà M, Krammer PH . The life and death of a B cell . Advances in Cancer Research . 86 . 195–225 . 2003 . 12374279 . 10.1016/S0065-230X(02)86006-7 . 9780120066865 .
• Ambrose CM . BAFF-R . Journal of Biological Regulators and Homeostatic Agents . 16 . 3 . 211–3 . 2003 . 12456020 .
• Bossen C, Schneider P . BAFF, APRIL and their receptors: structure, function and signaling . Seminars in Immunology . 18 . 5 . 263–75 . October 2006 . 16914324 . 10.1016/j.smim.2006.04.006 .
• Treml LS, Crowley JE, Cancro MP . BLyS receptor signatures resolve homeostatically independent compartments among naïve and antigen-experienced B cells . Seminars in Immunology . 18 . 5 . 297–304 . October 2006 . 16919470 . 10.1016/j.smim.2006.07.001 .
• Kalled SL . Impact of the BAFF/BR3 axis on B cell survival, germinal center maintenance and antibody production . Seminars in Immunology . 18 . 5 . 290–6 . October 2006 . 16931038 . 10.1016/j.smim.2006.06.002 .
• Mackay F, Leung H . The role of the BAFF/APRIL system on T cell function . Seminars in Immunology . 18 . 5 . 284–9 . October 2006 . 16931039 . 10.1016/j.smim.2006.04.005 .
• Schneider P, MacKay F, Steiner V, Hofmann K, Bodmer JL, Holler N, Ambrose C, Lawton P, Bixler S, Acha-Orbea H, Valmori D, Romero P, Werner-Favre C, Zubler RH, Browning JL, Tschopp J . BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth . The Journal of Experimental Medicine . 189 . 11 . 1747–56 . June 1999 . 10359578 . 2193079 . 10.1084/jem.189.11.1747 .
• Hartley JL, Temple GF, Brasch MA . DNA cloning using in vitro site-specific recombination . Genome Research . 10 . 11 . 1788–95 . November 2000 . 11076863 . 310948 . 10.1101/gr.143000 .
• Yan M, Brady JR, Chan B, Lee WP, Hsu B, Harless S, Cancro M, Grewal IS, Dixit VM . Identification of a novel receptor for B lymphocyte stimulator that is mutated in a mouse strain with severe B cell deficiency . Current Biology . 11 . 19 . 1547–52 . October 2001 . 11591325 . 10.1016/S0960-9822(01)00481-X . 13925100 . free . 2001CBio...11.1547Y .
• Rolink AG, Melchers F . BAFFled B cells survive and thrive: roles of BAFF in B-cell development . Current Opinion in Immunology . 14 . 2 . 266–75 . April 2002 . 11869903 . 10.1016/S0952-7915(02)00332-1 .
• Xu LG, Shu HB . TNFR-associated factor-3 is associated with BAFF-R and negatively regulates BAFF-R-mediated NF-kappa B activation and IL-10 production . Journal of Immunology . 169 . 12 . 6883–9 . December 2002 . 12471121 . 10.4049/jimmunol.169.12.6883 . free .
• Kim HM, Yu KS, Lee ME, Shin DR, Kim YS, Paik SG, Yoo OJ, Lee H, Lee JO . Crystal structure of the BAFF-BAFF-R complex and its implications for receptor activation . Nature Structural Biology . 10 . 5 . 342–8 . May 2003 . 12715002 . 10.1038/nsb925 . 11294267 . 10203/11495 . free .
• Liu Y, Hong X, Kappler J, Jiang L, Zhang R, Xu L, Pan CH, Martin WE, Murphy RC, Shu HB, Dai S, Zhang G . Ligand-receptor binding revealed by the TNF family member TALL-1 . Nature . 423 . 6935 . 49–56 . May 2003 . 12721620 . 10.1038/nature01543 . 2003Natur.423...49L . 4373708 . free .
• Gordon NC, Pan B, Hymowitz SG, Yin J, Kelley RF, Cochran AG, Yan M, Dixit VM, Fairbrother WJ, Starovasnik MA . BAFF/BLyS receptor 3 comprises a minimal TNF receptor-like module that encodes a highly focused ligand-binding site . Biochemistry . 42 . 20 . 5977–83 . May 2003 . 12755599 . 10.1021/bi034017g .

Notes and References

1. Thompson JS, Bixler SA, Qian F, Vora K, Scott ML, Cachero TG, Hession C, Schneider P, Sizing ID, Mullen C, Strauch K, Zafari M, Benjamin CD, Tschopp J, Browning JL, Ambrose C . BAFF-R, a newly identified TNF receptor that specifically interacts with BAFF . Science . 293 . 5537 . 2108–11 . September 2001 . 11509692 . 10.1126/science.1061965 . 2001Sci...293.2108T . 42673198 . free .
2. Yan M, Brady JR, Chan B, Lee WP, Hsu B, Harless S, Cancro M, Grewal IS, Dixit VM . Identification of a novel receptor for B lymphocyte stimulator that is mutated in a mouse strain with severe B cell deficiency . Current Biology . 11 . 19 . 1547–52 . October 2001 . 11591325 . 10.1016/S0960-9822(01)00481-X . 13925100 . free . 2001CBio...11.1547Y .
3. Web site: Entrez Gene: TNFRSF13C tumor necrosis factor receptor superfamily, member 13C.
4. Brink R . Regulation of B cell self-tolerance by BAFF . Seminars in Immunology . 18 . 5 . 276–83 . October 2006 . 16916609 . 10.1016/j.smim.2006.04.003 .
5. Rauch M, Tussiwand R, Bosco N, Rolink AG . Crucial role for BAFF-BAFF-R signaling in the survival and maintenance of mature B cells . PLOS ONE . 4 . 5 . e5456 . 2009-05-06 . 19421318 . 2673681 . 10.1371/journal.pone.0005456 . 2009PLoSO...4.5456R . free .