Limited access to antigen drives generation of early B cell memory while restraining the plasmablast response

Immunity. 2021 Sep 14;54(9):2005-2023.e10. doi: 10.1016/j.immuni.2021.08.017.


Cell fate decisions during early B cell activation determine the outcome of responses to pathogens and vaccines. We examined the early B cell response to T-dependent antigen in mice by single-cell RNA sequencing. Early after immunization, a homogeneous population of activated precursors (APs) gave rise to a transient wave of plasmablasts (PBs), followed a day later by the emergence of germinal center B cells (GCBCs). Most APs rapidly exited the cell cycle, giving rise to non-GC-derived early memory B cells (eMBCs) that retained an AP-like transcriptional profile. Rapid decline of antigen availability controlled these events; provision of excess antigen precluded cell cycle exit and induced a new wave of PBs. Fate mapping revealed a prominent contribution of eMBCs to the MBC pool. Quiescent cells with an MBC phenotype dominated the early response to immunization in primates. A reservoir of APs/eMBCs may enable rapid readjustment of the immune response when failure to contain a threat is manifested by increased antigen availability.

Keywords: B cells; cell fate decisions; germinal center B cells; germinal centers; humoral immune response; immunological memory; memory B cells; plasma cells; plasmablasts; scRNA-seq.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • B-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Germinal Center / immunology*
  • Immunity, Humoral / immunology*
  • Immunologic Memory / immunology*
  • Lymphocyte Activation / immunology*
  • Mice
  • Plasma Cells / immunology
  • Precursor Cells, B-Lymphoid / immunology