TY - JOUR
T1 - Single-cell analysis reveals dynamics of human B cell differentiation and identifies novel B and antibody-secreting cell intermediates
AU - Verstegen, Niels J. M.
AU - Pollastro, Sabrina
AU - Unger, Peter-Paul A.
AU - Marsman, Casper
AU - Elias, George
AU - Jorritsma, Tineke
AU - Streutker, Marij
AU - Bassler, Kevin
AU - Haendler, Kristian
AU - Rispens, Theo
AU - Schultze, Joachim L.
AU - Brinke, Anja Ten
AU - Beyer, Marc
AU - van Ham, S. Marieke
N1 - Funding Information: We thank the core facility at Sanquin, Erik Mul, Simon Tol, and Mark Hoogenboezem, for providing technical assistance. This research project was supported by a Landsteiner Foundation for Blood Transfusion Research grant (LSBR 1609) and a Product and process development grant for cellular products by Sanquin (PPOC17-34/L2263). MB was supported by the German Research Foundation (IRTG2168-272482170, SFB1454-432325352). Publisher Copyright: © Verstegen, Pollastro et al.
PY - 2023/3/1
Y1 - 2023/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85151528635&partnerID=8YFLogxK
U2 - https://doi.org/10.7554/elife.83578
DO - https://doi.org/10.7554/elife.83578
M3 - Article
C2 - 36861964
SN - 2050-084X
VL - 12
JO - eLife
JF - eLife
M1 - e83578
ER -