Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands; Synthetic Systems Biology and Nuclear Organization, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, Netherlands
Genomics and Immunoregulation, University of Bonn, Bonn, Germany
Kristian Haendler
Genomics and Immunoregulation, University of Bonn, Bonn, Germany; Platform for Single Cell Genomics and Epigenomics, German Center for Neurodegenerative Diseases (DZNE), University of Bonn, Bonn, Germany
Theo Rispens
Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
Joachim L Schultze
Genomics and Immunoregulation, University of Bonn, Bonn, Germany; Platform for Single Cell Genomics and Epigenomics, German Center for Neurodegenerative Diseases (DZNE), University of Bonn, Bonn, Germany
Anja ten Brinke
Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
Marc Beyer
Genomics and Immunoregulation, University of Bonn, Bonn, Germany; Platform for Single Cell Genomics and Epigenomics, German Center for Neurodegenerative Diseases (DZNE), University of Bonn, Bonn, Germany; Immunogenomics & Neurodegeneration, German Center for Neurodegenerative Diseases, Bonn, Germany
Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands; Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, Netherlands
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.
