The BLyS family of ligands and receptors: an archetype for niche-specific homeostatic regulation

Discovery and characterization of the tumor necrosis factor (TNF) family member B-lymphocyte stimulator (BLyS) has opened a novel chapter in the role of TNF family members in the homeostatic control of lymphocyte populations. BLyS and its sister cytokine APRIL (a proliferation-inducing ligand) act primarily as soluble trimers and serve to regulate the steady-state numbers of nearly all B-cell compartments. This homeostatic regulation is accomplished through the regulation of B-cell production rates, selection thresholds, and lifespan. Differential expression of the three BLyS receptors during differentiation and activation provides related yet distinct homeostatic niches for follicular, marginal zone, and memory B-cell subsets.