Restricted Clonality and Limited Germinal Center Reentry Characterize Memory B Cell Reactivation by Boosting

Cell. 2020 Jan 9;180(1):92-106.e11. doi: 10.1016/j.cell.2019.11.032. Epub 2019 Dec 19.


Repeated exposure to pathogens or their antigens triggers anamnestic antibody responses that are higher in magnitude and affinity than the primary response. These involve reengagement of memory B cell (MBC) clones, the diversity and specificity of which determine the breadth and effectiveness of the ensuing antibody response. Using prime-boost models in mice, we find that secondary responses are characterized by a clonality bottleneck that restricts the engagement of the large diversity of MBC clones generated by priming. Rediversification of mutated MBCs is infrequent within secondary germinal centers (GCs), which instead consist predominantly of B cells without prior GC experience or detectable clonal expansion. Few MBC clones, generally derived from higher-affinity germline precursors, account for the majority of secondary antibody responses, while most primary-derived clonal diversity is not reengaged detectably by boosting. Understanding how to counter this bottleneck may improve our ability to elicit antibodies to non-immunodominant epitopes by vaccination.

Keywords: affinity maturation; antibody response; clonal dynamics; germinal center memory B cell; immunological memory; influenza A virus; memory reactivation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / immunology
  • Animals
  • Antibody Formation / immunology
  • Antibody Formation / physiology
  • Antigens / immunology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • CHO Cells
  • Cell Line
  • Cricetulus
  • Female
  • Germinal Center / immunology*
  • Germinal Center / metabolism
  • Humans
  • Immunologic Memory / immunology*
  • Immunologic Memory / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Animal


  • Antigens