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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2004  |  Volume : 15  |  Issue : 2  |  Page : 155-156
B Lymphocyte Stimulator and Autoimmune Disease

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How to cite this article:
Wardle E N. B Lymphocyte Stimulator and Autoimmune Disease. Saudi J Kidney Dis Transpl 2004;15:155-6

How to cite this URL:
Wardle E N. B Lymphocyte Stimulator and Autoimmune Disease. Saudi J Kidney Dis Transpl [serial online] 2004 [cited 2021 Apr 14];15:155-6. Available from: https://www.sjkdt.org/text.asp?2004/15/2/155/32898

   What is BLys (BAFF)? Top

B Lymphocyte Stimulator (BLys), otherwise called B cell Activating Factor (BAFF), is a growth factor that helps B lymphocytes remain alive and mature into antibody producing plasma cells. [1] BLys promotes growth and expansion of B cells because it induces antiapoptotic bcl-2 and thus it protects B cells from death. It does not cause B cell prolife­ration. BLys is a member of the TNF-Receptor ligand family, [2] ie a member of a group of mediators that bind to TNFa-like receptors. Actually BLys has 3 possible receptors, [3] on B lymphocytes named B cell maturation antigen (BCMA), BAFF-R or Tac1.BLys is a glyco­protein on the cell membrane that is released by a furin protease to create the active 17 kDa soluble protein mediator, which is a potent B cell survival factor. BLys is involved in the formation of germinal centers in lymph nodes, in the generation of memory B cells and in the development of plasma cells. It is produced by dendritic cells, or by monocyte macro-phages or by T lymphocytes and thus it can act without the requirement for T helper cells. This feature carries the risk that, if production is unlimited, BLys will cause autoimmune B lymphocyte proliferation and formation of autoantibodies. In immunological terminology we say that BLys (BAFF) can "break B cell tolerance". [4]

   BLys and Systemic Lupus Erythematosus (SLE) Top

Mice that have been manipulated to produce transgenic BLys develop the features of SLE with elevated ds-DNA autoantibodies, rheu­matoid factor and appropriate renal histology. Furthermore, SLE [NZB x NZW] F1 mice or MRL-lpr/lpr mice have elevated plasma BLys at the time of disease onset. [5] Serum BLys is elevated in at least one third of SLE patients [6] and levels are often intermittently high in others. Since many of these patients will be taking an appreciable dose of corticosteroid, it may take time to establish the complete significance of this finding.

However, there must be more fundamental causes for the etiology of SLE, like a deficiency of T suppressor (regulatory) cells.

   Are There Other Pathologies Determined by BLys? Top

BLys is a recent discovery and it is inevitable that there will be speculations about possible actions in different pathologies. [7] How far is BLys relevant to Sjogren's syndrome, [8] another condition in which B cell autoantibodies manifest? Well, serum BLys is elevated in SS. Furthermore, the salivary glands are infil­trated by B cells with splenic marginal zone (MZ) phenotype; [8] these are B cells induced by BLys. This is a clue that the discovery of cells like this (in kidneys of SS, for example) may indicates a role for BLys (BAFF).

The LMP-1 antigen of Epstein Barr virus has been shown to promote switching of an immunoglobulin heavy chain so that IgG, IgA or IgE antibodies might be formed. [9] Initially, EB virus is though to infect B cells in the tonsillar epithelium. This action of LMP-1 works in conjunction with BLys that is induced by interleukin 10 induced by LMP­1. Once again, it means that antibody formation is independent of help from T cells.

Is there any other situation like this? We do not know the basic cause of IgA nephropathy except that there is formation of IgA immune complexes of special type. We do know that tonsillitis or upper respiratory tract infection with a variety of bacteria or viruses can cause synpharyngitic hematuria and exacerbation of IgA nephropathy. When dendritic cells on mucosae or in tonsils produce BLys, the classes switch of B cells in the mucosae results in the production of IgA antibodies. [10] Furthermore, dendritic cells exposed to vir­uses or bacteria release interferon-alpha that upregulate expression of BLys! So watch this space. At least we may have a new lead on the cause of IgA nephropathy. F Mackay has suggested that an antibody to BLys might help to control IgA nephropathy. [7] The antibody for BLys, called LymphoStat-B B, is already being examined for any potential in SLE therapy.

   References Top

1.Moore PA, Belvedere O, Orr A et al. BLyuc: member of the tumor necrosis factor family and B lymphocyte stimulator. Science 1999;285:260-3.  Back to cited text no. 1    
2.BodmerJL, Schneider P, Tschopp J. The molecular architecture of the TNF super­family. Trends Biochem Sci 2002;27:10-26.  Back to cited text no. 2    
3.Gross JA, Johnston J, Mudri S, et al. TAC1 and BCMA are receptors for a TNF homologue implicated in B cell auto-immune disease. Nature 2000;404:995-9.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]
4.Melchers F. Actions of BAFF in B cell maturation and its effects on the develop­ment of autoimmune disease. Ann Rheum Dis 2003;62:ii25-7.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.Zhang J, Roschke V, Baker KP, et al. A role for B lymphocyte stimulator in. J Immunol 2001;166:6-10.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Stohl W, Metyas S, Tan SM, et al. B lymphocyte stimulator overexpression in patients with systemic lupus erythematosus. Arthritis Rheum 2003;48:3475-86.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.Mackay F, Schneider P, Rennert P, Browning J. BAFF AND APRIL: a-tutorial in B cell survival. Ann Review Immunol 2003;21:231-64.  Back to cited text no. 7    
8.Groom J, Kalled SL, Cutler AH, et al. Association of BAFF/BLy overexpression and altered B cell differentiation with Sjogren,s syndrome. J Clin Invest 2002; 109:59-68.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.He B, Raab-Traub N, Casali P, Cerutti A. EBV encoded latent membrane protein-1 cooperates with BLy and April to induce T cell independent Ig heavy chain class switching. J Immunol 2003;171:5215-24.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]
10.Macpherson AJ, Lamarre A .BLysful inter­actions between DCs and B cells. Nat Immunol 2002;3(9):798-800.  Back to cited text no. 10    

Correspondence Address:
E Nigel Wardle
37 Princess Road, Camden, London NW1 8JS
United Kingdom
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PMID: 17642768

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