B-cell activating factor

B-cell activating factor (BAFF), also known as B-lymphocyte stimulator (BLyS), is a cytokine that plays a crucial role in B cell maturation, survival, and function. It is a member of the tumor necrosis factor (TNF) family, produced by a variety of cell types including monocytes, dendritic cells, and T cells.

Structure

BAFF is a type II transmembrane protein that exists in both membrane-bound and soluble forms. The soluble form is generated by proteolytic cleavage of the membrane-bound form. BAFF is a homotrimer in solution, and it can also form heterotrimers with a proliferation-inducing ligand (APRIL).

Function

BAFF plays a critical role in the survival and growth of B cells. It binds to three receptors on B cells: BAFF receptor (BAFF-R), transmembrane activator and CAML interactor (TACI), and B cell maturation antigen (BCMA). The binding of BAFF to these receptors triggers a series of intracellular signaling events that promote B cell survival and differentiation.

Clinical significance

Abnormal BAFF signaling has been implicated in the pathogenesis of several autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren's syndrome. Elevated levels of BAFF are found in the serum of patients with these diseases, and BAFF overexpression in mice leads to an autoimmune-like syndrome.

Several therapeutic agents targeting BAFF or its receptors are currently in development or in clinical use for the treatment of autoimmune diseases. These include belimumab, a monoclonal antibody against BAFF that is approved for the treatment of SLE, and atacicept, a fusion protein that inhibits both BAFF and APRIL.

See also

• B cell
• Cytokine
• Tumor necrosis factor
• Autoimmune disease