Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

BAFF: A fundamental survival factor for B cells

Key Points

  • B-cell-activating factor (BAFF) is a member of the tumour-necrosis factor (TNF) family.

  • BAFF is a trimeric membrane-bound or soluble factor that binds to three receptors — BCMA (B-cell maturation antigen), TACI (transmembrane activator and calcium-modulator and cyclophilin ligand (CAML) interactor) and BAFF-R (BAFF receptor) — which are all expressed on B cells. TACI and BAFF-R are also detected on T cells. BAFF and APRIL (a proliferation-inducing ligand) — another member of the TNF family — share TACI and BCMA.

  • BAFF is a survival factor for B cells that controls B-cell maturation. BAFF-deficient mice lack mature B cells. BAFF supports the survival of immature T2 B cells and, possibly, mature B cells, but not B1 B cells.

  • BAFF-R controls B-cell maturation and TACI controls B-cell homeostasis and T-cell-independent immune responses, whereas the role of BCMA is still unknown.

  • BAFF costimulates immune B-cell responses. Mice that are transgenic for BAFF have increased numbers of B cells — in particular, T2 and marginal-zone (MZ) B cells — and elevated levels of autoantibodies, and they progressively develop nephritis, as well as a Sjögren's-like syndrome.

  • MZ-like B cells have been detected in the inflamed tissues of BAFF-transgenic mice, which indicates a direct role for these cells in the pathogenesis of autoimmune disorders.

  • Elevated levels of BAFF have been detected in the serum of patients with various B-cell-mediated autoimmune disorders. BAFF has a role in the survival and/or growth of B-cell lymphomas.

  • BAFF is considered to be a prime therapeutic target.

Abstract

B-cell-activating factor of the tumour-necrosis-factor family (BAFF) enhances B-cell survival — a function that is indispensable for B-cell maturation — and has a role in enhancing immune responses. Moreover, the overexpression of BAFF results in severe autoimmune disorders in mice, and elevated serum levels of BAFF occur in some patients who have autoimmune diseases. The elucidation of the role of BAFF has set the stage for a new approach to the treatment of autoimmune disease.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Interactions between BAFF, APRIL and their receptors APRIL-R, BCMA, TACI and BAFF-R.
Figure 2: Survival signals during B-cell maturation.
Figure 3: BAFF-mediated B-cell maturation: possible mechanisms.
Figure 4: Model for the involvement of BAFF in peripheral immune tolerance.
Figure 5: The potential effects of elevated BAFF levels on MZ and B1 B cells.

References

  1. Grewal, I. S. & Flavell, R. A. CD40 and CD154 in cell-mediated immunity. Annu. Rev. Immunol. 16, 111–135 (1998).

    CAS  Article  PubMed  Google Scholar 

  2. Brown, M. A. & Hural, J. Functions of IL-4 and control of its expression. Crit. Rev. Immunol. 17, 1–32 (1997).

    CAS  Article  PubMed  Google Scholar 

  3. Stoddart, A., Fleming, H. E. & Paige, C. J. The role of the preBCR, the interleukin-7 receptor and homotypic interactions during B-cell development. Immunol. Rev. 175, 47–58 (2000).

    CAS  Article  PubMed  Google Scholar 

  4. Waldmann, T. A., Dubois, S. & Tagaya, Y. Contrasting roles of IL-2 and IL-15 in the life and death of lymphocytes: implications for immunotherapy. Immunity 14, 105–110 (2001).

    CAS  PubMed  Google Scholar 

  5. Lam, K. P., Kuhn, R. & Rajewsky, K. In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid death. Cell 90, 1073–1083 (1997).

    CAS  Article  PubMed  Google Scholar 

  6. Chao, D. T. & Korsmeyer, S. J. BCL-2 family: regulators of cell death. Annu. Rev. Immunol. 16, 395–419 (1998).

    CAS  Article  PubMed  Google Scholar 

  7. Strasser, A. et al. Enforced BCL2 expression in B-lymphoid cells prolongs antibody responses and elicits autoimmune disease. Proc. Natl Acad. Sci. USA 88, 8661–8665 (1991).This article shows the importance of Bcl-2 for B-cell survival. Mice that are transgenic for Bcl2 develop autoimmune disorders that are very similar to those of Baff -transgenic mice.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. Locksley, R. M., Killeen, N. & Lenardo, M. J. The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104, 487–501 (2001).

    CAS  PubMed  Google Scholar 

  9. Schneider, P. et al. BAFF, a novel ligand of the tumor-necrosis factor (TNF) family, stimulates B-cell growth. J. Exp. Med. 189, 1747–1756 (1999).This paper was the first to describe the discovery of BAFF and its role as a costimulator of B-cell activation.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. Shu, H.-B., Hu, W.-H. & Johnson, H. TALL-1 is a novel member of the TNF family that is down-regulated by mitogens. J. Leukocyte Biol. 65, 680–683 (1999).

    CAS  Article  PubMed  Google Scholar 

  11. Mukhopadhyay, A., Ni, J., Zhai, Y., Yu, G.-L. & Aggarwal, B. B. Identification and characterization of a novel cytokine, THANK, a TNF homologue that activates apoptosis, nuclear factor-κB and c-jun NH2-terminal kinase. J. Biol. Chem. 274, 15978–15981 (1999).

    CAS  Article  PubMed  Google Scholar 

  12. Moore, P. A. et al. BlyS: member of the tumor-necrosis factor family and B-lymphocyte stimulator. Science 285, 260–263 (1999).

    CAS  Article  PubMed  Google Scholar 

  13. Gross, J. A. et al. TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease. Nature 404, 995–999 (2000).

    CAS  Article  PubMed  Google Scholar 

  14. Karpusas, M. et al. Crystal structure of extracellular human BAFF, a TNF family member that stimulates B lymphocytes. J. Mol. Biol. 315, 1145–1154 (2002).

    CAS  Article  PubMed  Google Scholar 

  15. Liu, Y. et al. Crystal structure of sTALL-1 reveals a virus-like assembly of TNF ligands. Cell 108, 383–394 (2002).

    CAS  Article  PubMed  Google Scholar 

  16. Mackay, F. et al. Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J. Exp. Med. 190, 1697–1710 (1999).This work showed the development of autoimmunity in mice that overexpress BAFF and the up-regulation of Bcl-2 expression in B cells from Baff -transgenic animals.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. Nardelli, B. et al. Synthesis and release of B-lymphocyte stimulator from myeloid cells. Blood 97, 198–204 (2000).

    Article  Google Scholar 

  18. Hahne, M. et al. APRIL, a new ligand of the tumor-necrosis factor family, stimulates tumor growth. J. Exp. Med. 188, 1185–1190 (1998).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. Kelly, K., Manos, E., Jensen, G., Nadauld, L. & Jones, D. A. APRIL/TRDL-1, a tumor-necrosis factor-like ligand, stimulates cell death. Cancer Res. 60, 1021–1027 (2000).

    CAS  PubMed  Google Scholar 

  20. Bodmer, J. L., Schneider, P. & Tschopp, J. The molecular architecture of the TNF superfamily. Trends Biochem. Sci. 27, 19–26 (2002).

    CAS  Article  PubMed  Google Scholar 

  21. Lopez-Fraga, M., Fernandez, R., Albar, J. P. & Hahne, M. Biologically active APRIL is secreted following intracellular processing in the Golgi apparatus by furin convertase. EMBO Rep. 2, 945–951 (2001).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. Laabi, Y. et al. A new gene, BCM, on chromosome 16 is fused to the interleukin-2 gene by t(4;16) (q26;p13) translocation in a malignant T-cell lymphoma. EMBO Rep 11, 3897–3904 (1992).

    CAS  Article  Google Scholar 

  23. Madry, C. et al. The characterization of murine BCMA gene defines it as a new member of the tumor-necrosis factor receptor superfamily. Int. Immunol. 10, 1693–1702 (1998).

    CAS  Article  PubMed  Google Scholar 

  24. Von Buelow, G. U. & Bram, R. J. NF-AT activation induced by a CAML-interacting member of the tumor-necrosis factor receptor superfamily. Science 278, 138–141 (1997).

    Article  Google Scholar 

  25. Wu, Y. et al. Tumor-necrosis factor (TNF) receptor superfamily member TACI is a high-affinity receptor for TNF family members APRIL and BLyS. J. Biol. Chem. 275, 35478–35485 (2000).

    CAS  Article  PubMed  Google Scholar 

  26. Thompson, J. S. et al. BAFF-R, a novel TNF receptor that specifically interacts with BAFF. Science 293, 2108–2111 (2001).

    CAS  Article  PubMed  Google Scholar 

  27. Yan, M. et al. Identification of a novel receptor for B-lymphocyte stimulator that is mutated in a mouse strain with severe B-cell deficiency. Curr. Biol. 11, 1547–1552 (2001).

    CAS  Article  PubMed  Google Scholar 

  28. Wiley, S. R. et al. A novel TNF receptor family member binds TWEAK and is implicated in angiogenesis. Immunity 15, 837–846 (2001).

    CAS  Article  PubMed  Google Scholar 

  29. Gras, M. P. et al. BCMAp: an integral membrane protein in the golgi apparatus of human mature B lymphocytes. Int. Immunol. 7, 1093–1106 (1995).

    CAS  Article  PubMed  Google Scholar 

  30. Bradley, J. R., Thiru, S. & Pober, J. S. Disparate localization of 55-kd and 75-kd tumor-necrosis factor receptors in human endothelial cells. Am. J. Pathol. 146, 27–32 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Zhang, X. D., Franco, A. V., Nguyen, T., Gray, C. P. & Hersey, P. Differential localization and regulation of death and decoy receptors for TNF-related apoptosis-inducing ligand (TRAIL) in human melanoma cells. J. Immunol. 164, 3961–3970 (2000).

    CAS  Article  PubMed  Google Scholar 

  32. Thompson, J. S. et al. BAFF binds to the TNF receptor-like molecule BCMA and is important for maintaining the peripheral B-cell population. J. Exp. Med. 192, 129–135 (2000).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  33. Boilly, B., Vercoutter-Edouart, A. S., Hondermarck, H., Nurcombe, V. & Le Bourhis, X. FGF signals for cell proliferation and migration through different pathways. Cytokine Growth Factor Rev. 11, 295–302 (2000).

    CAS  Article  PubMed  Google Scholar 

  34. Wajant, H., Henkler, F. & Scheurich, P. The TNF-receptor-associated factor family: scaffold molecules for cytokine receptors, kinases and their regulators. Cell. Signal. 13, 389–400 (2001).

    CAS  Article  PubMed  Google Scholar 

  35. Hatzoglou, A. et al. TNF receptor family member BCMA (B-cell maturation) associates with TNF receptor-associated factor (TRAF)1, TRAF2, TRAF3 and activates NF-κB, Elk-1, c-jun N-terminal kinase and p38 mitogen-activated protein kinase. J. Immunol. 165, 1322–1330 (2000).

    CAS  Article  PubMed  Google Scholar 

  36. Shu, H.-B. & Johnson, H. B-cell maturation protein is a receptor for the tumor-necrosis factor family member TALL-1. Proc. Natl Acad. Sci. USA 97, 9156–9161 (2000).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. Marsters, S. A. et al. Interaction of the TNF homologues BLyS and APRIL with TNF receptor homologues BCMA and TACI. Curr. Biol. 10, 785–788 (2000).

    CAS  Article  PubMed  Google Scholar 

  38. Xia, X.-Z. et al. TACI is a TRAF-interacting receptor for TALL-1, a tumor-necrosis factor family member involved in B-cell regulation. J. Exp. Med. 192, 137–143 (2000).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. Senftleben, U. et al. Activation by IKKα of a second, evolutionary conserved, NF-κB signaling pathway. Science 293, 1495–1499 (2001).

    CAS  Article  PubMed  Google Scholar 

  40. Kaisho, T. et al. IκB kinase α is essential for mature B-cell development and function. J. Exp. Med. 193, 417–426 (2001).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  41. Grossmann, M. et al. The anti-apoptotic activities of rel and RelA required during B-cell maturation involve the regulation of Bcl-2. EMBO J. 19, 6351–6360 (2000).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  42. Yamada, T. et al. Abnormal immune function of hemopoietic cells from alymphoplasia (aly) mice, a natural strain with mutant NF-κB-inducing kinase. J. Immunol. 165, 804–812 (2000).

    CAS  Article  PubMed  Google Scholar 

  43. Do, R. K. et al. Attenuation of apoptosis underlies B-lymphocyte stimulator enhancement of humoral immune response. J. Exp. Med. 192, 953–964 (2000).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  44. Veis, D. J., Sorenson, C. M., Shutter, J. R. & Korsmeyer, S. J. Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys and hypopigmented hair. Cell 75, 229–240 (1993).

    CAS  Article  PubMed  Google Scholar 

  45. Loder, F. et al. B-cell development in the spleen takes place in discrete steps and is determined by the quality of B-cell receptor-derived signals. J. Exp. Med. 190, 75–89 (1999).This study established the distinction between T1 and T2 immature splenic B cells. It also showed the presence of a normal MZ B-cell population in the absence of mature B cells in some mutant mice, which indicates that T2 B cells might differentiate directly into MZ B cells.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  46. Allman, D. M., Ferguson, S. E., Lentz, V. M. & Cancro, M. P. Peripheral B-cell maturation. II. Heat stable antigenhi splenic B cells are an immature developmental intermediate in the production of long-lived marrow-derived B cells. J. Immunol. 151, 4431–4444 (1993).

    CAS  PubMed  Google Scholar 

  47. Batten, M. et al. BAFF mediates survival of peripheral immature B lymphocytes. J. Exp. Med. 192, 1453–1465 (2000).This article indicated a role for BAFF in B-cell maturation that was later confirmed in BAFF-deficient animals. This work also supports the possibility that T2 B cells are potential precursors of MZ B cells.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  48. Schiemann, B. et al. An essential role for BAFF in the normal development of B cells through a BCMA-independent pathway. Science 293, 2111–2114 (2001).The first description of BAFF-deficient mice. The maturation of B cells is arrested at the T1 B-cell stage in these animals.

    CAS  Article  PubMed  Google Scholar 

  49. Gross, J. A. et al. TACI–Ig neutralizes molecules critical for B-cell development and autoimmune disease: impaired B-cell maturation in mice lacking BLyS. Immunity 15, 289–302 (2001).

    CAS  Article  PubMed  Google Scholar 

  50. Schneider, P. et al. Maturation of marginal-zone and follicular B cells requires B-cell activating factor of the tumor-necrosis factor family and is independent of B-cell maturation antigen. J. Exp. Med. 194, 1691–1697 (2001).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  51. Xu, S. & Lam, K.-P. B-cell maturation protein, which binds the tumor-necrosis factor family members BAFF and APRIL, is dispensable for humoral immune responses. Mol. Cell. Biol. 21, 4067–4074 (2001).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  52. von Buelow, G.-U., van Deursen, J. M. & Bram, R. J. Regulation of the T-independent humoral response by TACI. Immunity 14, 573–582 (2001).

    Article  Google Scholar 

  53. Yan, M. et al. Activation and accumulation of B cells in TACI-deficient mice. Nature Immunol. 2, 638–643 (2001).

    CAS  Article  Google Scholar 

  54. Yu, G. et al. APRIL and TALL-1 and receptors BCMA and TACI: system for regulating humoral immunity. Nature Immunol. 1, 252–256 (2000).

    CAS  Article  Google Scholar 

  55. Amanna, I. J., Clise-Dwyer, K., Nashold, F. E., Hoag, K. A. & Hayes, C. E. A/WySnJ transitional B cells overexpress the chromosome 15 proapoptotic Blk gene and succumb to premature apoptosis. J. Immunol. 167, 6069–6072 (2001).

    CAS  Article  PubMed  Google Scholar 

  56. Harless, S. M. et al. Competition for BLyS-mediated signalling through Bcmd/BR3 regulates peripheral B-lymphocyte numbers. Curr. Biol. 11, 1986–1989 (2001).

    CAS  Article  PubMed  Google Scholar 

  57. Khare, S. D. et al. Severe B-cell hyperplasia and autoimmune disease in TALL-1 transgenic mice. Proc. Natl Acad. Sci. USA 97, 3370–3375 (2000).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  58. Matsumoto, M., Fu, Y.-X., Molina, H. & Chaplin, D. D. Lymphotoxin-α-deficient and TNF receptor-I-deficient mice define developmental and functional characteristics of germinal centers. Immunol. Rev. 156, 137–144 (1997).

    CAS  Article  PubMed  Google Scholar 

  59. Guinamard, R., Okigaki, M., Schlessinger, J. & Ravetch, J. V. Absence of marginal-zone B cells in Pyk-2-deficient mice define their role in the humoral response. Nature Immunol. 1, 37–41 (2000).

    Article  Google Scholar 

  60. Groom, J. et al. Association of BAFF/BLyS overexpression and altered B-cell differentiation with Sjögren's syndrome. J. Clin. Invest. 109, 59–68 (2002).This paper provides the first description of MZ-like B cells in inflamed tissues and the potential direct pathogenic role of this subset of B cells in autoimmunity.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  61. Yano, H. & Chao, M. V. Neurotrophin receptor structure and interactions. Pharm. Acta Helv. 74, 253–260 (2000).

    CAS  Article  PubMed  Google Scholar 

  62. Yan, M. et al. Identification of a receptor for BLyS demonstrates a crucial role in humoral immunity. Nature Immunol. 1, 37–41 (2000).

    CAS  Article  Google Scholar 

  63. Huard, B., Schneider, P., Mauri, D., Tschopp, J. & French, L. E. T-cell costimulation by the TNF ligand BAFF. J. Immunol. 167, 6225–6231 (2001).

    CAS  Article  PubMed  Google Scholar 

  64. Martin, F. & Kearney, J. F. B-cell subsets and the mature preimmune repertoire. Marginal-zone and B1 B cells as part of a 'natural immune memory'. Immunol. Rev. 175, 70–79 (2000).

    CAS  Article  PubMed  Google Scholar 

  65. Zhang, J. et al. A role for B-lymphocyte stimulator in systemic lupus erythematosus. J. Immunol. 166, 6–10 (2001).The first description of an association between high serum levels of BAFF and autoimmunity in humans.

    CAS  Article  PubMed  Google Scholar 

  66. Cheema, G. S., Roschke, V., Hilbert, D. M. & Stohl, W. Elevated serum B-lymphocyte stimulator levels in patients with systemic immune-based rheumatic diseases. Arthritis Rheum. 44, 1313–1319 (2001).

    CAS  Article  PubMed  Google Scholar 

  67. Jonsson, R., Haga, H.-J. & Gordon, T. P. in Arthritis and Allied Conditions (ed. Koopman, W.) 1826–1849 (Lea and Fabiger, Philadelphia, 2000).

    Google Scholar 

  68. Zeng, D., Lee, M.-K., Tung, J., Brendolan, A. & Strober, S. A role for CD1 in the pathogenesis of lupus in NZB/NZW mice. J. Immunol. 164, 5000–5004 (2000).

    CAS  Article  PubMed  Google Scholar 

  69. Amano, M. et al. CD1 expression defines subsets of follicular and marginal-zone B cells in the spleen: β2-microglobulin-dependent and -independent forms. J. Immunol. 161, 1710–1717 (1998).

    CAS  PubMed  Google Scholar 

  70. Grimaldi, C. M., Michael, D. J. & Diamond, B. Expansion and activation of a population of autoreactive marginal-zone B cells in a model of estrogen-induced lupus. J. Immunol. 167, 1886–1890 (2001).

    CAS  Article  PubMed  Google Scholar 

  71. Martin, F. & Kearney, J. F. Positive selection from newly formed to marginal-zone B cells depends on the rate of clonal production, CD19 and btk. Immunity 12, 39–49 (2000).The first article to indicate a possible alternative maturation pathway for polyreactive or potentially autoreactive B cells. These cells might preferentially differentiate into MZ B cells.

    CAS  Article  PubMed  Google Scholar 

  72. Cariappa, A. et al. The follicular versus marginal-zone B-lymphocyte cell-fate decision is regulated by aiolos, Btk and CD21. Immunity 14, 603–615 (2001).

    CAS  Article  PubMed  Google Scholar 

  73. Li, Y., Li, H. & Weigert, M. Autoreactive B cells in the marginal zone that express dual receptors. J. Exp. Med. 195, 181–188 (2002).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  74. Chen, X., Martin, F., Forbush, K. A., Perlmutter, R. M. & Kearney, J. K. Evidence for selection of a population of multi-reactive B cells into the splenic marginal zone. Int. Immunol. 9, 27–41 (1997).

    Article  PubMed  Google Scholar 

  75. Martin, F. & Kearney, J. F. CD21highIgMhigh splenic B cells enriched in the marginal zone: distinct phenotypes and functions. Curr. Top. Microbiol. Immunol. 246, 45–50 (1999).

    CAS  PubMed  Google Scholar 

  76. Kamata, T. et al. Increased frequency of surface IgA-positive plasma cells in the intestinal lamina propria and decreased IgA excretion in hyper IgA (HIGA) mice, a murine model of IgA nephropathy with hyperserum IgA. J. Immunol. 165, 1387–1394 (2000).

    CAS  Article  PubMed  Google Scholar 

  77. Briones, J., Timmerman, J. M., Hilbert, D. M. & Levy, R. BLyS and BLyS receptor expression in non-Hodgkin's lymphoma. Exp. Hematol. 30, 135–141 (2002).

    CAS  Article  PubMed  Google Scholar 

  78. Thieblemont, C., Berger, F. & Coiffier, B. Mucosa-associated lymphoid tissue lymphomas. Curr. Opin. Oncol. 7, 415–420 (1995).

    CAS  Article  PubMed  Google Scholar 

  79. Bannish, G., Fuentes-Panana, E. M., Cambier, J. C., Pear, W. S. & Monroe, J. G. Ligand-independent signaling functions for the B-lymphocyte antigen receptor and their role in positive selection during B lymphopoiesis. J. Exp. Med. 194, 1583–1596 (2001).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank C. R. Mackay, L. Girgis, S. Tangye, P. Schneider, I. R. Mackay, S. L. Kalled and J. Gommerman for critical reading of the manuscript and helpful suggestions.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Fabienne Mackay.

Related links

Related links

DATABASES

Cancer.gov

leukaemia

lymphoma

NHL

Entrez

Streptococcus pneumoniae

LocusLink

APRIL

BAFF

Baff

BAFF-R

Bak

Bcl-2

Bcl2

Bcl-xL

BCMA

Blk

CAML

CD3

CD20

CD40

CD40L

CD45

EDA

FN14

IFN-γ

Ikkα

IL-2

IL-4

IL-7

IL-10

IL-15

Lyn

NF-κB

NFGR

NIK

Pyk-2

Rel

Rela

TACI

TNF

TRAF

Trk

TWEAK

Vav

XEDAR

Medscape DrugInfo

Pneumovax

OMIM

rheumatoid arthritis

Sjögren's syndrome

SLE

Glossary

T HELPER 1/T HELPER 2

(TH1/TH2). At least two distinct subsets of activated CD4+ T cells have been described. TH1 cells produce IFN-γ, lymphotoxin and TNF, and support cell-mediated immunity. TH2 cells produce IL-4, IL-5 and IL-13, support humoral immunity and downregulate TH1 responses.

MARGINAL-ZONE B CELLS

Mature B cells that are phenotypically and functionally distinct from follicular B cells. They participate early in immune responses.

B1 COMPARTMENT

A population of self-renewing mature B cells that are enriched in pleural and peritoneal cavities. They recognize a restricted set of antigens, including self-antigens.

GERMINAL CENTRE

The structure that is formed by the expansion of antigen-activated B cells in the B-cell follicle. B cells in germinal centres proliferate and their immunoglobulin genes undergo somatic hypermutation. Cells exit the germinal centre as memory B cells or plasma cells.

SYSTEMIC LUPUS ERYTHEMATOSUS

(SLE). A human autoimmune disease of unknown aetiology, in which tissues and cells are damaged by pathogenic anti-bodies and immune-complex deposition. Generally, patients have abnormal T-cell and B-cell function.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Mackay, F., Browning, J. BAFF: A fundamental survival factor for B cells. Nat Rev Immunol 2, 465–475 (2002). https://doi.org/10.1038/nri844

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nri844

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing