Advances and challenges in investigating B-cells via single-cell transcriptomics

Single-cell RNA sequencing (scRNAseq) and Variable, Diversity, Joining (VDJ) profiling have improved our understanding of B-cells. Recent scRNAseq-based approaches have led to the discovery of intermediate B-cell states, including preplasma cells and pregerminal centre B-cells, as well as unveiling protective roles for B-cells within tertiary lymphoid structures in respiratory infections and cancers. These studies have improved our understanding of transcriptional and epigenetic control of B-cell development and of atypical and memory B-cell differentiation. Advancements in temporal profiling in parallel with transcriptomic and VDJ sequencing have consolidated our understanding of the trajectory of B-cell clones over the course of infection and vaccination. Challenges remain in studying B-cell states across tissues in humans, in relating spatial location with B-cell phenotype and function, in examining antibody isotype switching events, and in unequivocal determination of clonal relationships. Nevertheless, ongoing multiomic assessments and studies of cellular interactions within tissues promise new avenues for improving humoral immunity and combatting autoimmune conditions.