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Antibodies from primary humoral responses modulate the recruitment of naive B cells during secondary responses. 2022
Jeroen M J Tas, and
Ja-Hyun Koo, and
Ying-Cing Lin, and
Zhenfei Xie, and
Jon M Steichen, and
Abigail M Jackson, and
Blake M Hauser, and
Xuesong Wang, and
Christopher A Cottrell, and
Jonathan L Torres, and
John E Warner, and
Kathrin H Kirsch, and
Stephanie R Weldon, and
Bettina Groschel, and
Bartek Nogal, and
Gabriel Ozorowski, and
Sandhya Bangaru, and
Nicole Phelps, and
Yumiko Adachi, and
Saman Eskandarzadeh, and
Michael Kubitz, and
Dennis R Burton, and
Daniel Lingwood, and
Aaron G Schmidt, and
Usha Nair, and
Andrew B Ward, and
William R Schief, and
Facundo D Batista
The Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA 02139, USA.
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.
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