4.7 Article

Clonal structure, stability and dynamics of human memory B cells and circulating plasmablasts

Journal

NATURE IMMUNOLOGY
Volume 23, Issue 7, Pages 1076-+

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41590-022-01230-1

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Funding

  1. European Research Council [885539 ENGRAB]
  2. Fondation Louis-Jeantet
  3. Wenner-Gren Foundation fellowship

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This study provides a systematic description of the structure, stability, and dynamics of the human memory B cell pool, and suggests that memory B cells play a crucial role in the generation of plasma cells.
Memory B cells persist for a lifetime and rapidly differentiate into antibody-producing plasmablasts and plasma cells upon antigen re-encounter. The clonal relationship and evolution of memory B cells and circulating plasmablasts is not well understood. Using single-cell sequencing combined with isolation of specific antibodies, we found that in two healthy donors, the memory B cell repertoire was dominated by large IgM, IgA and IgG2 clonal families, whereas IgG1 families, including those specific for recall antigens, were of small size. Analysis of multiyear samples demonstrated stability of memory B cell clonal families and revealed that a large fraction of recently generated plasmablasts was derived from long-term memory B cell families and was found recurrently. Collectively, this study provides a systematic description of the structure, stability and dynamics of the human memory B cell pool and suggests that memory B cells may be active at any time point in the generation of plasmablasts. Lanzavecchia and colleagues use single-cell B cell receptor sequencing to examine the clonal structure, stability and dynamics of the B cell repertoire and the relationship between memory B cells and newly generated plasma cells in humans.

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