APRIL and TALL-1 and receptors BCMA and TACI: system for regulating humoral immunity

Abstract

We report that the tumor neurosis factor homolog APRIL (a proliferation-inducing ligand) stimulates in vitro proliferation of primary B and T cells and increases spleen weight due to accumulation of B cells in vivo. APRIL functions via binding to BCMA (B cell maturation antigen) and TACI (transmembrane activator and CAML-interactor) and competes with TALL-I (also called BLyS or BAFF) for receptor binding. Soluble BCMA and TACI specifically prevent binding of APRIL and block APRIL-stimulated proliferation of primary B cells. BCMA-Fc also inhibits production of antibodies against keyhole limpet hemocyanin and Pneumovax in mice, indicating that APRIL and/or TALL-I signaling via BCMA and/or TACI are required for generation of humoral immunity. Thus, APRIL-TALL-I and BCMA-TACI form a two ligands-two receptors pathway involved in stimulation of B and T cell function.

Cutting Edge: Germinal Centers Formed in the Absence of B Cell-Activating Factor Belonging to the TNF Family Exhibit Impaired Maturation and Function

“…The data were consistent with previous reports (19,22,23) and showed that, over time, the primary anti-NP response was significantly reduced with BAFF inhibition when compared with control animals (Fig. 4).…”

“…4, right panel). These data are consistent with previously published reports using BAFF inhibitors (19,22).…”

“…Briefly, total and highaffinity NP-specific Ab were captured on NP 22 -BSA and NP 3 -BSA (Biosearch Technologies)-coated plates, respectively. To elaborate anti-NP specific L chain, a biotin-labeled rat anti-mAb Ls136 was used.…”

Lymphoma cell adhesion-induced expression of B cell-activating factor of the TNF family in bone marrow stromal cells protects non-Hodgkin's B lymphoma cells from apoptosis

“…11 B cell-activating factor exerts its effect by binding to three known receptors: transmembrane activator and calcium modulator cyclophilin ligand interactor (TACI), B-cell maturation antigen (BCMA) and BAFF-receptor/BLyS receptor 3 (BAFF-R). 8,[12][13][14][15] BAFF-R and BCMA expression are restricted to B cells, whereas TACI is found on both B cells and activated T cells. BAFF receptors appear to be expressed on immunoglobulin-positive B cells but not on immunoglobulin-negative pre-and pro-B cells.…”

Rheumatoid arthritis fibroblast‐like synoviocytes express BCMA and are stimulated by APRIL

“…APRIL was shown to have a remarkable capacity to stimulate both solid and lymphoid tumor growth (21,22). Currently, 2 TNF receptor family members, TACI and BCMA, have been shown to bind to APRIL with high affinity (23).…”