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Single-cell analysis reveals dynamics of human B cell differentiation and identifies novel B and antibody-secreting cell intermediates.


Authors: Niels J M Verstegen, Sabrina Pollastro, Peter-Paul A Unger, Casper Marsman, George Elias, Tineke Jorritsma, Marij Streutker, Kevin Bassler, Kristian Haendler, Theo Rispens, Joachim L Schultze, Anja Ten Brinke, Marc Beyer, S Marieke van Ham

Differentiation of B cells into antibody-secreting cells (ASCs) is a key process to generate protective humoral immunity. A detailed understanding of the cues controlling ASC differentiation is important to devise strategies to modulate antibody formation. Here, we dissected differentiation trajectories of human naive B cells into ASCs using single-cell RNA sequencing. By comparing transcriptomes of B cells at different stages of differentiation from an in vitro model with ex vivo B cells and ASCs, we uncovered a novel pre-ASC population present ex vivo in lymphoid tissues. For the first time, a germinal-center-like population is identified in vitro from human naive B cells and possibly progresses into a memory B cell population through an alternative route of differentiation, thus recapitulating in vivo human GC reactions. Our work allows further detailed characterization of human B cell differentiation into ASCs or memory B cells in both healthy and diseased conditions.

© 2023, Verstegen, Pollastro et al.

PMID: 36861964

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