Encyclopedia of Signaling Molecules

Living Edition
| Editors: Sangdun Choi

BAFF/BLyS Family

  • Arpita Myles
  • Jean L. Scholz
  • Michael P. Cancro
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-6438-9_101556-1



APRIL: A proliferation-inducing ligand

Synonyms: TNFSF13a; TALL-2; TRDL-1; CD256

BAFF/BLyS: B cell-activating factor of the TNF family/B lymphocyte stimulator

Synonyms: TNFSF13b; TALL-1; zTNF-4; THANK; CD257


BCMA: B cell maturation antigen

Synonyms: TNFRSF13a; TNFRSF17; CD269

TACI: Transmembrane activator and calcium modulator and cyclophilin ligand interactor

Synonyms: TNFRSF13b; CD267

BAFFR/BR3: BAFF receptor/BLyS receptor 3

Synonyms: TNFRSF13c; Bcmd; CD268


The BAFF/BLyS family includes two cytokine ligands and three receptors, all of which are members of the TNF/TNF receptor superfamily. Members of the BLyS family play critical and varied regulatory roles among cells of the B lymphocyte lineage: they control the selection and survival of pre-immune B cells, govern aspects of selection and differentiation among activated B cells, and impact formation and survival of antibody-secreting plasma cells. General features of these ligands and receptors...


Germinal Center Common Variable Immune Deficiency Furin Cleavage Fibroblastic Reticular Cell BLyS Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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The BLyS family of receptors and ligands plays a pivotal role in maintaining peripheral homeostasis of B cells in both mice and humans. Their influence on differentiation and maintenance of antigen-experienced subsets is also beginning to be appreciated. Apart from regulating selection and life span, the BLyS/BR3 axis is relevant in autoimmunity and is a current therapeutic target.


  1. Amanna IJ, Slifka MK. Mechanisms that determine plasma cell lifespan and the duration of humoral immunity. Immunol Rev. 2010;236:125–38.CrossRefPubMedGoogle Scholar
  2. Anderson SM, Hannum LG, Shlomchik MJ. Memory B cell survival and function in the absence of secreted antibody and immune complexes on follicular dendritic cells. J Immunol. 2006;176(8):4515–9.CrossRefPubMedGoogle Scholar
  3. Bossen C, Schneider P. BAFF, APRIL and their receptors: structure, function and signaling. Semin Immunol. 2006;18(5):263–75.CrossRefPubMedGoogle Scholar
  4. Cancro MP. Peripheral B-cell maturation: the intersection of selection and homeostasis. Immunol Rev. 2004;197:89–101.CrossRefPubMedGoogle Scholar
  5. Cancro MP, D'Cruz DP, Khamashta MA. The role of B lymphocyte stimulator (BLyS) in systemic lupus erythematosus. J Clin Invest. 2009;119(5):1066–73.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Chatham WW, Wallace DJ, Stohl W, Latinis KM, Manzi S, McCune WJ, Tegzova D, McKay JD, Avila-Armengol HE, Utset TO, Zhong ZJ, Hough DR, Freimuth WW, Migone TS, Group B-S. Effect of belimumab on vaccine antigen antibodies to influenza, pneumococcal, and tetanus vaccines in patients with systemic lupus erythematosus in the BLISS-76 trial. J Rheumatol. 2012;39(8):1632–40.CrossRefPubMedGoogle Scholar
  7. Coquery CM, Erickson LD. Regulatory roles of the tumor necrosis factor receptor BCMA. Crit Rev Immunol. 2012;32:287–305.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Cremasco V, Woodruff MC, Onder L, Cupovic J, Nieves-Bonilla JM, Schildberg FA, Chang J, Cremasco F, Harvey CJ, Wucherpfennig K, Ludewig B, Carroll MC, Turley SJ. B cell homeostasis and follicle confines are governed by fibroblastic reticular cells. Nat Immunol. 2014;2014(10):973–81.CrossRefGoogle Scholar
  9. Darce JR, Arendt BK, Wu X, Jelinek DF. Regulated expression of BAFF-binding receptors during human B cell differentiation. J Immunol. 2007;179(11):7276–86.CrossRefPubMedGoogle Scholar
  10. Goenka R, Scholz JL, Sindhava VJ, Cancro MP. New roles for the BLyS/BAFF family in antigen-experienced B cell niches. Cytokine Growth Factor Rev. 2014;25(2):107–13.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Karnell JL, Ettinger R. The interplay of IL-21 and BAFF in the formation and maintenance of human B cell memory. Front Immunol. 2012;3:2.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Naradikian MS, Hao Y, Cancro MP. Age-associated B cells: key mediators of both protective and autoreactive humoral responses. Immunol Rev. 2016;269(1):118–29.CrossRefPubMedGoogle Scholar
  13. Oropallo MA, Kiefer K, Marshak-Rothstein A, Cancro MP. Beyond transitional selection: New roles for BLyS in peripheral tolerance. Drug Dev Res. 2011;72:779–87.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Rickert RC, Jellusova J, Miletic AV. Signaling by the tumor necrosis factor receptor superfamily in B-cell biology and disease. Immunological Reviews. 2011;244(1):115–33.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Romberg N, Chamberlain N, Saadoun D, Gentile M, Kinnunen T, Ng YS, Virdee M, Menard L, Cantaert T, Morbach H, Rachid R, Martinez-Pomar N, Matamoros N, Geha R, Grimbacher B, Cerutti A, Cunningham-Rundles C, Meffre E. CVID-associated TACI mutations affect autoreactive B cell selection and activation. J Clin Invest. 2013;123(10):4283–93.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Sindhava VJ, Scholz JL, Cancro MP. Roles for BLyS family members in meeting the distinct homeostatic demands of innate and adaptive B cells. Front Immunol. 2013;4:37.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Srivastava B, Quinn 3rd WJ, Hazard K, Erikson J, Allman D. Characterization of marginal zone B cell precursors. J Exp Med. 2005;202(9):1225–34.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Stadanlick JE, Cancro MP. Unraveling the warp and weft of B cell fate. Immunity. 2006;25(3):395–6.CrossRefPubMedGoogle Scholar
  19. Stohl W, Scholz JL, Cancro MP. Targeting BLyS in rheumatic disease: the sometimes-bumpy road from bench to bedside. Curr Opin Rheumatol. 2011;23(3):305–10.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Vincent FB, Saulep-Easton D, Figgett WA, Fairfax KA, Mackay F. The BAFF/APRIL system: emerging functions beyond B cell biology and autoimmunity. Cytokine Growth Factor Rev. 2013;24(3):203–15.CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media LLC 2016

Authors and Affiliations

  • Arpita Myles
    • 1
  • Jean L. Scholz
    • 1
  • Michael P. Cancro
    • 1
  1. 1.Department of Pathology and Laboratory Medicine, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA