Distinct stage-specific transcriptional states of B cells in human tonsillar tissue

ABSTRACT B cells within secondary lymphoid tissues encompass a diverse range of activation states and multiple maturation processes that reflect antigen recognition and transition through the germinal center (GC) reaction, in which mature B cells differentiate into memory and antibody-secreting cells (ASCs). Here, using single-cell RNA-seq, we identify distinct activation and maturation profiles of B cells within and outside the GC reaction in human secondary lymphoid tissue. In particular, we identify a distinct, previously uncharacterized CCL4 / CCL3 chemokine-expressing B-cell population with an expression pattern consistent with BCR/CD40 activation. Furthermore, we present a computational method leveraging regulatory network inference and pseudotemporal modeling to identify upstream transcription factor modulation along the GC to ASC maturation axis. Our dataset provides valuable insight into the diverse functional profiles and maturation processes that B cells undergo within secondary lymphoid tissues and will be a useful resource on which to base further studies into the B-cell immune compartment. Highlights scRNA-seq of human tonsillar B cells identifies distinct activation and maturation phenotypes. Identification of a chemokine-expressing B-cell population in the human tonsil with a BCR and CD40 co-stimulatory gene signature. Transcription factor regulatory network analysis identifies MYC and REL as predicted regulators of chemokine expression in the chemokine-expressing B-cell population. Trajectory inference with gene and regulatory network modeling implicates novel transcription factors in the GC-to-ASC transition.