Advertisement

BAFF Receptor Deficiency

  • Cristian R. Smulski
  • Patricia Odermatt
  • Hermann EibelEmail author
Chapter
Part of the Rare Diseases of the Immune System book series (RDIS)

Abstract

BAFF receptor (BAFF = B cell-activating factor of the TNF family) is a main pro-survival receptor expressed by human B cells. BAFFR deficiency is caused by a homologous deletion within the BAFFR gene (TNFRSF13C). The mutation causes a severe block of B cell development at the stage of immature B cells leading to agammaglobulinemia, impaired humoral immune responses, and immunodeficiency (Warnatz et al., Proc Natl Acad Sci USA 106:13945–50, 2009). In this chapter, we will discuss the main characteristics, the expression, and the signaling properties of BAFF receptor to provide the background information which is needed to explaining the clinical and immunological consequences of BAFFR deficiency and of BAFFR missense mutations.

Keywords

BAFF BAFF receptor TNF B cells Cytokines TNF receptor 

References

  1. 1.
    Pieper K, Rizzi M, Speletas M, Smulski CR, Sic H, Kraus H, Salzer U, Fiala GJ, Schamel WW, Lougaris V, Plebani A, Hammarstrom L, Recher M, Germenis AE, Grimbacher B, Warnatz K, Rolink AG, Schneider P, Notarangelo LD, Eibel H. A common single nucleotide polymorphism impairs B-cell activating factor receptor’s multimerization, contributing to common variable immunodeficiency. J Allergy Clin Immunol. 2014;133:1222–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Ng LG, Sutherland AP, Newton R, Qian F, Cachero TG, Scott ML, Thompson JS, Wheway J, Chtanova T, Groom J, Sutton IJ, Xin C, Tangye SG, Kalled SL, Mackay F, Mackay CR. B cell-activating factor belonging to the TNF family (BAFF)-R is the principal BAFF receptor facilitating BAFF costimulation of circulating T and B cells. J Immunol. 2004;173:807–17.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Rodig SJ, Shahsafaei A, Li B, Mackay CR, Dorfman DM. BAFF-R, the major B cell-activating factor receptor, is expressed on most mature B cells and B-cell lymphoproliferative disorders. Hum Pathol. 2005;36:1113–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Naismith JH, Sprang SR. Modularity in the TNF-receptor family. Trends Biochem Sci. 1998;23:74–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Do RK, Hatada E, Lee H, Tourigny MR, Hilbert D, Chen-Kiang S. Attenuation of apoptosis underlies B lymphocyte stimulator enhancement of humoral immune response. J Exp Med. 2000;192:953–64.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Smulski CR, Kury P, Seidel LM, Staiger HS, Edinger AK, Willen L, Seidl M, Hess H, Salzer U, Rolink AG, Rizzi M, Schneider P, Eibel H. BAFF- and TACI-dependent processing of BAFFR by ADAM proteases regulates the survival of B cells. Cell Rep. 2017;18:2189–202.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Gross JA, Johnston J, Mudri S, Enselman R, Dillon SR, Madden K, Xu W, Parrish-Novak J, Foster D, Lofton-Day C, Moore M, Littau A, Grossman A, Haugen H, Foley K, Blumberg H, Harrison K, Kindsvogel W, Clegg CH. TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease. Nature. 2000;404:995–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Mantchev GT, Cortesao CS, Rebrovich M, Cascalho M, Bram RJ. TACI is required for efficient plasma cell differentiation in response to T-independent Type 2 antigens. J Immunol. 2007;179:2282–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Ozcan E, Garibyan L, Lee JJ, Bram RJ, Lam KP, Geha RS. Transmembrane activator, calcium modulator, and cyclophilin ligand interactor drives plasma cell differentiation in LPS-activated B cells. J Allergy Clin Immunol. 2009;123:1277–86.e5.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Tsuji S, Cortesao C, Bram RJ, Platt JL, Cascalho M. TACI deficiency impairs sustained Blimp-1 expression in B cells decreasing long-lived plasma cells in the bone marrow. Blood. 2011;118:5832–9.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    O’Connor BP, Raman VS, Erickson LD, Cook WJ, Weaver LK, Ahonen C, Lin LL, Mantchev GT, Bram RJ, Noelle RJ. BCMA is essential for the survival of long-lived bone marrow plasma cells. J Exp Med. 2004;199:91–8.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Rowland SL, Leahy KF, Halverson R, Torres RM, Pelanda R. BAFF receptor signaling aids the differentiation of immature B cells into transitional B cells following tonic BCR signaling. J Immunol. 2010;185:4570–81.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Smith SH, Cancro MP. Cutting edge: B cell receptor signals regulate BLyS receptor levels in mature B cells and their immediate progenitors. J Immunol. 2003;170:5820–3.PubMedCrossRefGoogle Scholar
  14. 14.
    Hobeika E, Levit-Zerdoun E, Anastasopoulou V, Pohlmeyer R, Altmeier S, Alsadeq A, Dobenecker MW, Pelanda R, Reth M. CD19 and BAFF-R can signal to promote B-cell survival in the absence of Syk. EMBO J. 2015;34:925–39.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Levit-Zerdoun E, Becker M, Pohlmeyer R, Wilhelm I, Maity PC, Rajewsky K, Reth M, Hobeika E. Survival of Igalpha-deficient mature B cells requires BAFF-R function. J Immunol. 2016;196:2348–60.PubMedCrossRefGoogle Scholar
  16. 16.
    Bossen C, Cachero TG, Tardivel A, Ingold K, Willen L, Dobles M, Scott ML, Maquelin A, Belnoue E, Siegrist CA, Chevrier S, Acha-Orbea H, Leung H, Mackay F, Tschopp J, Schneider P. TACI, unlike BAFF-R, is solely activated by oligomeric BAFF and APRIL to support survival of activated B cells and plasmablasts. Blood. 2008;111:1004–12.PubMedCrossRefGoogle Scholar
  17. 17.
    Shu HB, Hu WH, Johnson H. TALL-1 is a novel member of the TNF family that is down-regulated by mitogens. J Leukoc Biol. 1999;65:680.PubMedCrossRefGoogle Scholar
  18. 18.
    Schneider P, Mackay CR, 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. J Exp Med. 1999;189:1747–56.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Moore PA, Belvedere O, Orr A, Pieri K, LaFleur DW, Feng P, Soppet D, Charters M, Gentz R, Parmelee D, Li Y, Galperina O, Giri J, Roschke V, Nardelli B, Carrell J, Sosnovtseva S, Greenfield W, Ruben SM, Olsen HS, Fikes J, Hilbert DM. BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. Science. 1999;285:260–3.PubMedCrossRefGoogle Scholar
  20. 20.
    Hahne M, Kataoka T, Schröter M, Hofmann K, Irmler M, Bodmer JL, Schneider P, Bornand T, Holler N, French LE, Sordat B, Rimoldi D, Tschopp J. APRIL, a new ligand of the tumor necrosis factor family stimulates tumor cell growth. J Exp Med. 1998;188:1185–90.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Liu Y, Hong X, Kappler J, Jiang L, Zhang R, Xu L, Pan C, Martin WE, Murphy RC, Shu HB, Dai S, Zhang G. Ligand–receptor binding revealed by the TNF family member TALL-1. Nature. 2003;423:49–56.PubMedCrossRefGoogle Scholar
  22. 22.
    Liu Y, Xu L, Opalka N, Kappler J, Shu HB, Zhang B. Crystal structure of sTALL-1 reveals a virus-like assembly of TNF family ligands. Cell Press. 2002;108:383–94.Google Scholar
  23. 23.
    Cachero TG, Schwartz IM, Qian F, Day ES, Bossen C, Ingold K, Tardivel A, Krushinskie D, Eldredge J, Silvian L, Lugovskoy A, Farrington GK, Strauch K, Schneider P, Whitty A. Formation of virus-like clusters is an intrinsic property of the tumor necrosis factor family member BAFF (B cell activating factor). Biochemistry. 2005;45:2006–13.CrossRefGoogle Scholar
  24. 24.
    Karpusas M, Cachero TG, Qian F, Sjodin AB, Mullen C, Strauch K, Hsu YM, Kalled SL. Crystal structure of extracellular human BAFF, a TNF family member that stimulates B lymphocytes. J Mol Biol. 2002;315:1145–54.PubMedCrossRefGoogle Scholar
  25. 25.
    Ingold K, Zumsteg A, Tardivel A, Huard B, Steiner QG, Cachero TG, Qiang F, Gorelik L, Kalled SL, Acha-Orbea H, Rennert PD, Tschopp J, Schneider P. Identification of proteoglycans as the APRIL-specific binding partners. J Exp Med. 2005;201:1375–83.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Kimberley FC, van Bostelen L, Cameron K, Hardenberg G, Marquart JA, Hahne M, Medema JP. The proteoglycan (heparan sulfate proteoglycan) binding domain of APRIL serves as a platform for ligand multimerization and cross-linking. FASEB J. 2009;23:1584–95.PubMedCrossRefGoogle Scholar
  27. 27.
    Schuepbach-Mallepell S, Das D, Willen L, Vigolo M, Tardivel A, Lebon L, Kowalczyk-Quintas C, Nys J, Smulski C, Zheng TS, Maskos K, Lammens A, Jiang X, Hess H, Tan SL, Schneider P. Stoichiometry of heteromeric BAFF and APRIL cytokines dictates their receptor binding and signaling properties. J Biol Chem. 2015;290:16330–42.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Nardelli B, Belvedere O, Roschke V, Moore PA, Olsen HS, Migone TS, Sosnovtseva S, Carrell J, Feng P, Giri J, Hilbert DM. Synthesis and release of B-lymphocyte stimulator from myeloid cells. Blood J. 2001;97:198–204.CrossRefGoogle Scholar
  29. 29.
    Thangarajh M, Masterman T, Helgeland L, Rot U, Jonsson MV, Eide GE, Pirskanen R, Hillert J, Jonsson R. The thymus is a source of B-cell-survival factors-APRIL and BAFF-in myasthenia gravis. J Neuroimmunol. 2006;178:161–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Litinskiy MB, Nardelli B, Hilbert DM, He B, Schaffer A, Casali P, Cerutti A. DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL. Nat Immunol. 2002;3:822–9.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Kreuzaler M, Rauch M, Salzer U, Birmelin J, Rizzi M, Grimbacher B, Plebani A, Lougaris V, Quinti I, Thon V, Litzman J, Schlesier M, Warnatz K, Thiel J, Rolink AG, Eibel H. Soluble BAFF levels inversely correlate with peripheral B cell numbers and the expression of BAFF receptors. J Immunol. 2012;188:497–503.PubMedCrossRefGoogle Scholar
  32. 32.
    Claudio E, Brown K, Park S, Wang H, Siebenlist U. BAFF-induced NEMO-independent processing of NF-kappa B2 in maturing B cells. Nat Immunol. 2002;3:958–65.PubMedCrossRefGoogle Scholar
  33. 33.
    Kayagaki N, Yan M, Seshasayee D, Wang H, Lee W, French DM, Grewal IS, Cochran AG, Gordon NC, Yin J, Starovasnik MA, Dixit VM. BAFF/BLyS receptor 3 binds the B cell survival factor BAFF ligand through a discrete surface loop and promotes processing of NF-kappaB2. Immunity. 2002;17:515–24.PubMedCrossRefGoogle Scholar
  34. 34.
    Zhang Q, Lenardo MJ, Baltimore D. 30 Years of NF-kappaB: a blossoming of relevance to human pathobiology. Cell. 2017;168:37–57.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Vallabhapurapu S, Karin M. Regulation and function of NF-kappaB transcription factors in the immune system. Annu Rev Immunol. 2009;27:693–733.PubMedCrossRefGoogle Scholar
  36. 36.
    Willmann KL, Klaver S, Dogu F, Santos-Valente E, Garncarz W, Bilic I, Mace E, Salzer E, Conde CD, Sic H, Majek P, Banerjee PP, Vladimer GI, Haskologlu S, Bolkent MG, Kupesiz A, Condino-Neto A, Colinge J, Superti-Furga G, Pickl WF, van Zelm MC, Eibel H, Orange JS, Ikinciogullari A, Boztug K. Biallelic loss-of-function mutation in NIK causes a primary immunodeficiency with multifaceted aberrant lymphoid immunity. Nat Commun. 2014;5:5360.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Liao G, Zhang M, Harhaj EW, Sun SC. Regulation of the NF-kappaB-inducing kinase by tumor necrosis factor receptor-associated factor 3-induced degradation. J Biol Chem. 2004;279:26243–50.PubMedCrossRefGoogle Scholar
  38. 38.
    Ling L, Cao Z, Goeddel DV. NF-kappaB-inducing kinase activates IKK-alpha by phosphorylation of Ser-176. Proc Natl Acad Sci U S A. 1998;95:3792–7.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Xiao G, Harhaj EW, Sun SC. NF-kappaB-inducing kinase regulates the processing of NF-kappaB2 p100. Mol Cell. 2001;7:401–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Amir RE, Haecker H, Karin M, Ciechanover A. Mechanism of processing of the NF-kappa B2 p100 precursor: identification of the specific polyubiquitin chain-anchoring lysine residue and analysis of the role of NEDD8-modification on the SCF(beta-TrCP) ubiquitin ligase. Oncogene. 2004;23:2540–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Dejardin E, Droin NM, Delhase M, Haas E, Cao Y, Makris C, Li ZW, Karin M, Ware CF, Green DR. The lymphotoxin-beta receptor induces different patterns of gene expression via two NF-kappaB pathways. Immunity. 2002;17:525–35.PubMedCrossRefGoogle Scholar
  42. 42.
    Sun SC, Ganchi PA, Beraud C, Ballard DW, Greene WC. Autoregulation of the NF-kappa B transactivator RelA (p65) by multiple cytoplasmic inhibitors containing ankyrin motifs. Proc Natl Acad Sci U S A. 1994;91:1346–50.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Derudder E, Dejardin E, Pritchard LL, Green DR, Korner M, Baud V. RelB/p50 dimers are differentially regulated by tumor necrosis factor-alpha and lymphotoxin-beta receptor activation: critical roles for p100. J Biol Chem. 2003;278:23278–84.PubMedCrossRefGoogle Scholar
  44. 44.
    Yilmaz ZB, Weih DS, Sivakumar V, Weih F. RelB is required for Peyer’s patch development: differential regulation of p52-RelB by lymphotoxin and TNF. EMBO J. 2003;22:121–30.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Li T, Morgan MJ, Choksi S, Zhang Y, Kim YS, Liu ZG. MicroRNAs modulate the noncanonical transcription factor NF-kappaB pathway by regulating expression of the kinase IKKalpha during macrophage differentiation. Nat Immunol. 2010;11:799–805.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Hu H, Wu X, Jin W, Chang M, Cheng X, Sun SC. Noncanonical NF-kappaB regulates inducible costimulator (ICOS) ligand expression and T follicular helper cell development. Proc Natl Acad Sci U S A. 2011;108:12827–32.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Maurer U, Charvet C, Wagman AS, Dejardin E, Green DR. Glycogen synthase kinase-3 regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1. Mol Cell. 2006;21:749–60.PubMedCrossRefGoogle Scholar
  48. 48.
    Razani B, Zarnegar B, Ytterberg AJ, Shiba T, Dempsey PW, Ware CF, Loo JA, Cheng G. Negative feedback in noncanonical NF-kappaB signaling modulates NIK stability through IKKalpha-mediated phosphorylation. Sci Signal. 2010;3:ra41.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Hu H, Brittain GC, Chang JH, Puebla-Osorio N, Jin J, Zal A, Xiao Y, Cheng X, Chang M, Fu YX, Zal T, Zhu C, Sun SC. OTUD7B controls non-canonical NF-kappaB activation through deubiquitination of TRAF3. Nature. 2013;494:371–4.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Schweighoffer E, Vanes L, Nys J, Cantrell D, McCleary S, Smithers N, Tybulewicz VL. The BAFF receptor transduces survival signals by co-opting the B cell receptor signaling pathway. Immunity. 2013;38:475–88.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Jellusova J, Miletic AV, Cato MH, Lin WW, Hu Y, Bishop GA, Shlomchik MJ, Rickert RC. Context-specific BAFF-R signaling by the NF-kappaB and PI3K pathways. Cell Rep. 2013;5:1022–35.PubMedCrossRefGoogle Scholar
  52. 52.
    Mattila PK, Feest C, Depoil D, Treanor B, Montaner B, Otipoby KL, Carter R, Justement LB, Bruckbauer A, Batista FD. The actin and tetraspanin networks organize receptor nanoclusters to regulate B cell receptor-mediated signaling. Immunity. 2013;38:461–74.PubMedCrossRefGoogle Scholar
  53. 53.
    Keppler SJ, Gasparrini F, Burbage M, Aggarwal S, Frederico B, Geha RS, Way M, Bruckbauer A, Batista FD. Wiskott-Aldrich syndrome interacting protein deficiency uncovers the role of the co-receptor CD19 as a generic Hub for PI3 kinase signaling in B cells. Immunity. 2015;43:660–73.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Fruman DA, Cantley LC. Phosphoinositide 3-kinase in immunological systems. Semin Immunol. 2002;14:7–18.PubMedCrossRefGoogle Scholar
  55. 55.
    Okada T, Maeda A, Iwamatsu A, Gotoh K, Kurosaki T. BCAP: the tyrosine kinase substrate that connects B cell receptor to phosphoinositide 3-kinase activation. Immunity. 2000;13:817–27.PubMedCrossRefGoogle Scholar
  56. 56.
    Aiba Y, Kameyama M, Yamazaki T, Tedder TF, Kurosaki T. Regulation of B-cell development by BCAP and CD19 through their binding to phosphoinositide 3-kinase. Blood. 2008;111:1497–503.PubMedCrossRefGoogle Scholar
  57. 57.
    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. 2001;293:2108–11.PubMedCrossRefGoogle Scholar
  58. 58.
    Jellusova J, Rickert RC. The PI3K pathway in B cell metabolism. Crit Rev Biochem Mol Biol. 2016;51:359–78.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Patke A, Mecklenbrauker I, Erdjument-Bromage H, Tempst P, Tarakhovsky A. BAFF controls B cell metabolic fitness through a PKC beta- and Akt-dependent mechanism. J Exp Med. 2006;203:2551–62.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Woodland RT, Fox CJ, Schmidt MR, Hammerman PS, Opferman JT, Korsmeyer SJ, Hilbert DM, Thompson CB. Multiple signaling pathways promote B lymphocyte stimulator dependent B-cell growth and survival. Blood. 2008;111:750–60.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Hoffmann FS, Kuhn PH, Laurent SA, Hauck SM, Berer K, Wendlinger SA, Krumbholz M, Khademi M, Olsson T, Dreyling M, Pfister HW, Alexander T, Hiepe F, Kumpfel T, Crawford HC, Wekerle H, Hohlfeld R, Lichtenthaler SF, Meinl E. The immunoregulator soluble TACI is released by ADAM10 and reflects B cell activation in autoimmunity. J Immunol. 2015;194:542–52.PubMedCrossRefGoogle Scholar
  62. 62.
    Mesin L, Ersching J, Victora GD. Germinal center B cell dynamics. Immunity. 2016;45:471–82.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Kräutler NJ, Suan D, Butt D, Bourne K, Hermes JR, Chan TD, Sundling C, Kaplan W, Schofield P, Jackson J, Basten A, Christ D, Brink R. Differentiation of germinal center B cells into plasma cells is initiated by high-affinity antigen and completed by Tfh cells. J Exp Med. 2017;214:1259.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Warnatz K, Salzer U, Rizzi M, Fischer B, Gutenberger S, Bohm J, Kienzler AK, Pan-Hammarstrom Q, Hammarstrom L, Rakhmanov M, Schlesier M, Grimbacher B, Peter HH, Eibel H. B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans. Proc Natl Acad Sci U S A. 2009;106:13945–50.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Mackay F, Woodcock SA, Lawton P, Ambrose C, Baetscher M, Schneider P, Tschopp J, Browning JL. Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med. 1999;190:1697–710.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Steri M, Orru V, Idda ML, Pitzalis M, Pala M, Zara I, Sidore C, Faa V, Floris M, Deiana M, Asunis I, Porcu E, Mulas A, Piras MG, Lobina M, Lai S, Marongiu M, Serra V, Marongiu M, Sole G, Busonero F, Maschio A, Cusano R, Cuccuru G, Deidda F, Poddie F, Farina G, Dei M, Virdis F, Olla S, Satta MA, Pani M, Delitala A, Cocco E, Frau J, Coghe G, Lorefice L, Fenu G, Ferrigno P, Ban M, Barizzone N, Leone M, Guerini FR, Piga M, Firinu D, Kockum I, Lima Bomfim I, Olsson T, Alfredsson L, Suarez A, Carreira PE, Castillo-Palma MJ, Marcus JH, Congia M, Angius A, Melis M, Gonzalez A, Alarcon Riquelme ME, da Silva BM, Marchini M, Danieli MG, Del Giacco S, Mathieu A, Pani A, Montgomery SB, Rosati G, Hillert J, Sawcer S, D’Alfonso S, Todd JA, Novembre J, Abecasis GR, Whalen MB, Marrosu MG, Meloni A, Sanna S, Gorospe M, Schlessinger D, Fiorillo E, Zoledziewska M, Cucca F. Overexpression of the cytokine BAFF and autoimmunity risk. N Engl J Med. 2017;376:1615–26.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Castigli E, Wilson SA, Garibyan L, Rachid R, Bonilla F, Schneider L, Geha RS. TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat Genet. 2005;37:829–34.PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Salzer U, Chapel HM, Webster AD, Pan-Hammarstrom Q, Schmitt-Graeff A, Schlesier M, Peter HH, Rockstroh JK, Schneider P, Schaffer AA, Hammarstrom L, Grimbacher B. Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans. Nat Genet. 2005;37:820–8.PubMedCrossRefGoogle Scholar
  69. 69.
    Seshasayee D, Valdez P, Yan M, Dixit VM, Tumas D, Grewal IS. Loss of TACI causes fatal lymphoproliferation and autoimmunity, establishing TACI as an inhibitory BLyS receptor. Immunity. 2003;18:279–88.PubMedCrossRefGoogle Scholar
  70. 70.
    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. Curr Biol. 2001b;11:1547–52.PubMedCrossRefGoogle Scholar
  71. 71.
    von Bülow G, van Deursen JM, Bram RJ. Regulation of the T-independent humoral response by TACI. Immunity. 2001;14:573–82.CrossRefGoogle Scholar
  72. 72.
    Batten M, Fletcher C, Ng LG, Groom J, Wheway J, Laabi Y, Xin X, Schneider P, Tschopp J, Mackay CR, Mackay F. TNF deficiency fails to protect BAFF transgenic mice against autoimmunity and reveals a predisposition to B cell lymphoma. J Immunol. 2004;172:812–22.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Puga I, Cols M, Barra CM, He B, Cassis L, Gentile M, Comerma L, Chorny A, Shan M, Xu W, Magri G, Knowles DM, Tam W, Chiu A, Bussel JB, Serrano S, Lorente JA, Bellosillo B, Lloreta J, Juanpere N, Alameda F, Baro T, de Heredia CD, Toran N, Catala A, Torrebadell M, Fortuny C, Cusi V, Carreras C, Diaz GA, Blander JM, Farber CM, Silvestri G, Cunningham-Rundles C, Calvillo M, Dufour C, Notarangelo LD, Lougaris V, Plebani A, Casanova JL, Ganal SC, Diefenbach A, Arostegui JI, Juan M, Yague J, Mahlaoui N, Donadieu J, Chen K, Cerutti A. B cell-helper neutrophils stimulate the diversification and production of immunoglobulin in the marginal zone of the spleen. Nat Immunol. 2011;13:170–80.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Magri G, Miyajima M, Bascones S, Mortha A, Puga I, Cassis L, Barra CM, Comerma L, Chudnovskiy A, Gentile M, Llige D, Cols M, Serrano S, Arostegui JI, Juan M, Yague J, Merad M, Fagarasan S, Cerutti A. Innate lymphoid cells integrate stromal and immunological signals to enhance antibody production by splenic marginal zone B cells. Nat Immunol. 2014;15:354–64.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Losi CG, Silini A, Fiorini C, Soresina A, Meini A, Ferrari S, Notarangelo LD, Lougaris V, Plebani A. Mutational analysis of human BAFF receptor TNFRSF13C (BAFF-R) in patients with common variable immunodeficiency. J Clin Immunol. 2005;25:496–502.PubMedCrossRefGoogle Scholar
  76. 76.
    Hildebrand JM, Luo Z, Manske MK, Price-Troska T, Ziesmer SC, Lin W, Hostager BS, Slager SL, Witzig TE, Ansell SM, Cerhan JR, Bishop GA, Novak AJ. A BAFF-R mutation associated with non-Hodgkin lymphoma alters TRAF recruitment and reveals new insights into BAFF-R signaling. J Exp Med. 2010;207:2569–79.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Kutukculer N, Gulez N, Karaca NE, Aksu G, Berdeli A. Three different classifications, B lymphocyte subpopulations, TNFRSF13B (TACI), TNFRSF13C (BAFF-R), TNFSF13 (APRIL) gene mutations, CTLA-4 and ICOS gene polymorphisms in Turkish patients with common variable immunodeficiency. J Clin Immunol. 2012;32:1165–79.PubMedCrossRefGoogle Scholar
  78. 78.
    Martin F, Kearney JF. B1 cell: similarities and differences with other B cell subsets. Curr Opin Immunol. 2001;13:195–201.PubMedCrossRefGoogle Scholar
  79. 79.
    Pillai S, Cariappa A, Moran ST. Positive selection and lineage commitment during peripheral B-lymphocyte development. Immunol Rev. 2004;197:206–18.PubMedCrossRefGoogle Scholar
  80. 80.
    Hardy RR, Hayakawa K. Perspectives on fetal derived CD5+ B1 B cells. Eur J Immunol. 2015;45:2978–84.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Jacobs HM, Thouvenel CD, Leach S, Arkatkar T, Metzler G, Scharping NE, Kolhatkar NS, Rawlings DJ, Jackson SW. Cutting edge: BAFF promotes autoantibody production via TACI-dependent activation of transitional B cells. J Immunol. 2016;196:3525–31.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Rahman ZS, Rao SP, Kalled SL, Manser T. Normal induction but attenuated progression of germinal center responses in BAFF and BAFF-R signaling-deficient mice. J Exp Med. 2003;198:1157–69.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Benson MJ, Dillon SR, Castigli E, Geha RS, Xu S, Lam KP, Noelle RJ. Cutting edge: the dependence of plasma cell and independence of memory B cell on BAFF and APRIL. J Immunol. 2008;180:3655–9.PubMedCrossRefGoogle Scholar
  84. 84.
    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. 2009;4:e5456.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Furie R, Petri M, Zamani O, Cervera R, Wallace DJ, Tegzova D, Sanchez-Guerrero J, Schwarting A, Merrill JT, Chatham WW, Stohl W, Ginzler EM, Hough DR, Zhong ZJ, Freimuth W, van Vollenhoven RF. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum. 2011;63:3918–30.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Stohl W, Hiepe F, Latinis KM, Thomas M, Scheinberg MA, Clarke A, Aranow C, Wellborne FR, Abud-Mendoza C, Hough DR, Pineda L, Migone TS, Zhong ZJ, Freimuth WW, Chatham WW. Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in patients with systemic lupus erythematosus. Arthritis Rheum. 2012;64:2328–37.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    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. 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;39:1632–40.PubMedCrossRefGoogle Scholar
  88. 88.
    van Vollenhoven RF, Kinnman N, Vincent E, Wax S, Bathon J. Atacicept in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase II, randomized, placebo-controlled trial. Arthritis Rheum. 2011;63:1782–92.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Cristian R. Smulski
    • 1
  • Patricia Odermatt
    • 1
  • Hermann Eibel
    • 1
    Email author
  1. 1.Faculty of Medicine, Center for Chronic ImmunodeficiencyMedical Center—University of Freiburg, University of FreiburgFreiburgGermany

Personalised recommendations