B cell activating factor

BAFF as a B-cell activating factor was first described by several research groups at the end of the 1990s. Therefore, other names such as BLyS (B Lymphocyte Stimulator), TALL-1 (TNF- and ApoL related leukocyte expressed ligand 1), THANK (TNF homolog activates apoptosis, nuclear factor- B and c- Jun NH2 terminal kinase), zTNF4 (z- tumor necrosis factor 4) and TNFSF 13b (TNF- Superfamily Member 13b) can also be found in the literature (Gross et al. 2000).

BAFF is the acronym for "B-cell activating factor". BAFF is a trimeric membrane-bound or also soluble cytokine (glycoprotein) consisting of 285 amino acids, a member of the tumor necrosis factor superfamily.

BAFF is mainly expressed in spleen, lymph nodes and in peripheral leukocytes. BAFF is produced by myeloproliferative cells such as monocytes, macrophages and dendritic cells, as well as by stromal cells of the lymph nodes and spleen (Hase et al. 2004). In addition, neutrophil granulocytes are also important producers of BAFF. BAFF is an important survival factor for B cells.

BAFF is considered an essential factor for the survival of B cells. The gylyc protein seems to be of particular importance during the maturation and differentiation of the B cell into a plasma cell. It can be assumed that the formation of BAFF is triggered by cytokines such as IFNα, IFNγ as well as IL-10 and other growth factors.

BAFF-binding receptors are BAFFreceptor (BAFF-R), B cell maturation antigen (BCMA), and the transmembrane activator and CAML interactor(TACI) (Treml et al. 2008). All three receptors are expressed on B- lymphocytes, TACI has also been detected on activated T- lymphocytes.

Note: The TNF superfamily currently consists of about 40 identified ligand and receptor proteins. These can influence and modify growth as well as differentiation and survival of cells and apoptosis of target cells. The interaction occurs mostly via membrane-bound or -soluble ligands of the TNF superfamily with corresponding membrane-bound or soluble receptors (Aggarwal 2003).

The interaction of BAFF and BAFF-R is considered responsible for the function of BAFF as the survival factor for B cells. However, costimmulation of T- cells mostly via BAFF- R has also been shown (Mackay et al. 2003). Conversely, studies show a reduction in B-cell numbers and antibody production when BAFF is inhibited.

Another ligand of the TNF family is APRIL (A proliferation inducing ligand). Its role in the immune system is not yet fully understood (Treml et al. 2008). Like BAFF, APRIL is mainly expressed by myeloid cells and has so far been detected mainly in tumor tissues. It has been shown that APRIL increases the number of B lymphocytes circulating in the periphery and has a suppressive effect on the T cell-triggered immune response (Castigli et al. 2004).

APRIL interacts with the receptors BCMA and TACI as well as with proteoglycans of the cell membrane, but not with BAFF-R (Treml et al. 2008). There is increasing evidence that BAFF plays a crucial role in the development of autoimmune diseases and lymphomas.

If a B cell receives only a weak signal for apoptosis, apoptosis is prevented by a physiologically present BAFF concentration and the B cell can mature (Bannish et al. 2001). A B- cell receives a strong apoptosis signal when it binds with high affinity to an auto-antigen. The physiologically present BAFF concentration cannot compensate for this, so that the cell goes into apoptosis. However, if there is an overproduction of BAFF in the organism and thus strong apoptosis signals are also suppressed, it can happen that autoreactive B cells mature and autoimmunity is triggered. (Mackay et al. 2002).

Furthermore, BAFF presents itself as a potential diagnostic marker and target of therapeutic treatment approaches. In the meantime, an increased BAFF concentration in serum could be detected in a number of autoimmune diseases such as rheumatoid arthritis, Sjögren 's syndrome as well as systemic sclerosis and systemic lupus erythematosus (SLE) (Matsushita et al. 2006). In part, as in systemic sclerosis, the level of BAFF measured in serum correlates with disease severity (Mariette et al. 2003). Increased BAFF levels have also been detected in the sera of patients with systemic lupus erythematosus, the level of which correlates with the degree of disease activity (Matsushita et al. 2006). It is assumed that increased BAFF levels are related to activated B cells and plasma cells.

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