Temporal dynamics and genomic programming of plasma cell fates
Vijay, G. K. M.; Zhou, M.; Thakkar, K.; Rothrauff, A.; Chawla, A.; Chen, D.; Lau, L.; Habib, P.; Chetal, K.; Chhibbar, P.; Fan, J.; Das, J.; Joglekar, A. V.; Borghesi, L.; Salomonis, N.; Xu, H.; Singh, H.
Show abstract
Affinity-matured plasma cells (PCs) of varying lifespans are generated through a germinal center (GC) response. The developmental dynamics and genomic programs of antigen-specific PC precursors remain to be elucidated. Using a model antigen, we demonstrate biphasic generation of PC precursors, with those generating long-lived bone marrow PCs preferentially produced in the 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 PCs, based on extended antigen encounters followed by reduced antigen availability.
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