The BLyS family: toward a molecular understanding of B cell homeostasis

Abstract

The B Lymphocyte Stimulator (BLyS) family of ligands and receptors regulates humoral immunity by controlling B lymphocyte survival and differentiation. Herein, we review the ligands and receptors of this family, their biological functions, and the biochemical processes through which they operate. Pre-immune B lymphocytes rely on BLyS signaling for their survival, whereas antigen experienced B lymphocytes generally interact more avidly with a homologous cytokine, A Proliferation Inducing Ligand (APRIL). The molecular basis for signaling via the three BLyS family receptors reveals complex interplay with other B lymphocyte signaling systems, affording the integration of selective and homeostatic processes. As our understanding of this system advances, molecular targets for manipulating humoral immunity in both health and disease should be revealed.

Fig. 1

Receptor Expression and Cytokine Dependence. B cells in pre-immune subsets express both BR3 and TACI, but only BLyS is required for their normal development. Antigenic stimuli result in changes in receptor expression. T cell dependent stimuli favor BR3 expression and lead to germinal center reactions, while T cell independent stimuli favor TACI expression on the resulting short-lived plasma cells. Although all recently activated B cells express one or more BLyS receptors, the exact roles played by BLyS and/or APRIL in their survival or differentiation has not been fully interrogated. Long-lived bone marrow plasma cells express BCMA, and require APRIL for normal survival. Memory cells express TACI, but are largely independent of either BLyS or APRIL