FIG 1.

BAFF system molecules. (A) BAFF system molecules are composed of two ligands (BAFF and APRIL) and three receptors (BAFF-R, TACI, and BCMA). BAFF and APRIL are primarily expressed by myeloid cells. BAFF is initially synthesized as a membrane-bound form (mBAFF). BAFF also has a soluble form (sBAFF). The soluble form is produced by the cleavage of mBAFF with furin convertase. sBAFF exists in a homotrimeric (3-mer) or oligomeric (60-mer) form. The cleavage of APRIL by furin convertase occurs in the Golgi apparatus or on the cell membrane. Similar to BAFF, soluble APRIL forms a homotrimer or partners with heparan sulfate proteoglycan (HSPG) to form multimers. Membrane-bound BAFF-R (mBAFF-R) is shed by ADAM10 and ADAM17 following BAFF stimulation. TACI can also be found in a soluble form (sTACI) after the cleavage of mTACI by ADAM10 and ADAM17. The activity of ADAM17 requires the stimulation of B cells by 60-mer BAFF. mBCMA is processed by γ-secretase. The cleaved ectodomains of the three receptors may function as soluble decoy receptors (sBAFF-R, sTACI, and sBCMA) for BAFF and APRIL. (B) BAFF engagement of BAFF-R is essential for the survival and development of B cells beyond the immature T1 B cell stage. TACI is mostly expressed on marginal zone (MZ) B cells, follicular (FO) B cells, and plasma cells. BCMA expression is increased on plasmablasts and plasma cells. BAFF and APRIL also act on macrophages to stimulate the expression of molecules associated with the inflammatory M1 phenotype. BM, bone marrow; BCR, B cell receptor; DC, dendritic cell; iNOS, inducible nitric oxide synthase; TNFα, tumor necrosis factor alpha.