Temporal dynamics and genomic programming of plasma cell fates

Bone marrow plasma cells (BMPCs) of varying lifespans are generated through a germinal center response (GC). The developmental dynamics and genomic programs of antigen-specific plasma cell (PC) precursors remain to be elucidated. Using a model antigen, we demonstrate biphasic generation of BMPC precursors, with those generating long-lived PCs preferentially produced in late phase of GC response. Clonal tracing using scRNA-seq+BCR-seq in spleen and bone marrow compartments, coupled with adoptive transfer experiments, reveal a novel PC transition state that gives rise to functionally competent PC precursors, the latter undergo clonal expansion, dependent on inducible expression of TIGIT. We propose a model for the proliferation and programming of precursors of long-lived BMPCs, based on extended antigen encounters. Overall design: Splenic and bone marrow CD138+ cells or subsets were isolated using positive selection or flow cytometry based sorting from C57BL6/J mice immunized with NP-KLH, alum and LPS at indicated days post-immunization (d.p.i.)