Antibodies from primary humoral responses modulate the recruitment of naive B cells during secondary responses

Immunity. 2022 Oct 11;55(10):1856-1871.e6. doi: 10.1016/j.immuni.2022.07.020. Epub 2022 Aug 4.

Abstract

Vaccines generate high-affinity antibodies by recruiting antigen-specific B cells to germinal centers (GCs), but the mechanisms governing the recruitment to GCs on secondary challenges remain unclear. Here, using preclinical SARS-CoV and HIV mouse models, we demonstrated that the antibodies elicited during primary humoral responses shaped the naive B cell recruitment to GCs during secondary exposures. The antibodies from primary responses could either enhance or, conversely, restrict the GC participation of naive B cells: broad-binding, low-affinity, and low-titer antibodies enhanced recruitment, whereas, by contrast, the high titers of high-affinity, mono-epitope-specific antibodies attenuated cognate naive B cell recruitment. Thus, the directionality and intensity of that effect was determined by antibody concentration, affinity, and epitope specificity. Circulating antibodies can, therefore, be important determinants of antigen immunogenicity. Future vaccines may need to overcome-or could, alternatively, leverage-the effects of circulating primary antibodies on subsequent naive B cell recruitment.

Keywords: BG18; HIV; RBD; SARS-CoV; antibody; germinal center; humoral immunity.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens
  • B-Lymphocytes*
  • Epitopes
  • Germinal Center*
  • Immunity, Humoral
  • Mice

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens
  • Epitopes