B cells require B-cell-activating factor (BAFF) for normal B lymphocyte development. BAFF, also known as BLyS, TALL-1, zTNF4 and THANK, is a member of the tumour necrosis factor (TNF) superfamily (TNFSF13B), produced and secreted mainly by myeloid cells (macrophages, monocytes and dendritic cells), but also by non-lymphoid cell types (salivary gland epithelial cells, astrocytes and fibroblast-like synoviocytes) and epithelial cells including bronchial and nasal epithelial cells [2–4].

It is expressed as a type II transmembrane Vemurafenib mw protein (biologically active 17-kDa molecule), and levels of BAFF are upregulated by interferon (INF)-γ, interleukin (IL)-10 Palbociclib concentration and CD40 ligand produced during inflammation and/or chronic infections [5]. BAFF is an important regulator of peripheral B-cell survival, maturation, immunoglobulin production and immunoglobulin class-switch recombination (CSR) [2]. Increased release of BAFF

may lead to the emergence of autoreactivity, especially in those with genetic susceptibility. Thus, in animal models, overexpression of BAFF leads to B-cell hyperplasia, lymphoproliferation, hypergammaglobulinemia and symptoms of autoimmunity. Conversely, BAFF-deficient animals exhibit defects in peripheral B-cell maturation and decreased levels of immunoglobulins [4, 6]. Recently, BAFF has emerged as an important regulator of T-cell-mediated reactions as well [7, 8]. Although BAFF is supposed to play an important role in the pathogenesis of autoimmune diseases, high levels in other conditions such as allergic diseases, infections and malignancies suggest a role of BAFF also there (Table 1). BAFF activates IgG, IgA and IgE isotype switching in B cells. CSR is a biological mechanism by which activated B cells (plasma cells) change their antibody production from one isotype to another, for example, from IgM to IgG. Naive mature B

cells produce both IgM and IgD, which contain the PAK5 first two heavy chain segments of the immunoglobulins. For making a new isotype of antibody by CSR, B cells require 2 signals. The first signal normally comes through T-cell cytokines (IL-4, IL-10, IL-13 and TGF-β), while the second is delivered by engagement of CD40 on B cells [9]. In addition, BAFF impacts on this process by one of its specific receptors, called TACI [9, 10]. To produce IgG, IgA or IgE antibodies, the constant region of the immunoglobulin heavy chain changes while the variable regions, and therefore antigen specificity, stay the same. This allows different daughter cells from the same activated B cell to produce antibodies of different isotypes or subtypes (e.g. IgG1 and IgG2).