APRIL Drives a Coordinated but Diverse Response as a Foundation for Plasma Cell Longevity

Ab-secreting cells survive in niche microenvironments, but cellular responses driven by particular niche signals are incompletely defined. The TNF superfamily member a proliferation-inducing ligand (APRIL) can support the maturation of transitory plasmablasts into long-lived plasma cells. In this study, we explore the biological programs established by APRIL in human plasmablasts. Under conditions allowing the maturation of ex vivo- or in vitro-generated plasmablasts, we find that APRIL drives activation of ERK, p38, and JNK, accompanied by a classical NF-kappa B response and activation of the AKT/FOX01 pathway. Time-course gene expression data resolve coordinated transcriptional responses propagated via immediate early genes and NF-KB targets and converging onto modules of genes enriched for MYC targets and metabolism/cell growth-related pathways. This response is shared between APRIL and an alternate TNF superfamily member CD4OL but is not a feature of alternative niche signals delivered by IFN-a or SDF1. However, APRIL and CD4OL responses also diverge. CD4OL drives expression of genes related to the activated B cell state whereas APRIL does not. Thus, APRIL establishes a broad foundation for plasma cell longevity with features of cellular refueling while being uncoupled from support of the B cell state.

Automated summary

This study explores the role of APRIL in human plasmablasts and finds that APRIL can promote plasma cell maturation and longevity. APRIL achieves this through the regulation of multiple signaling pathways and transcriptional responses, sharing some similarities with CD4OL but also showing distinct differences.