National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
AI144462
米国
Bill & Melinda Gates Foundation
INV-002916
米国
Bill & Melinda Gates Foundation
OPP1196345
米国
Bill & Melinda Gates Foundation
INV-008813
米国
引用
ジャーナル: Immunity / 年: 2022 タイトル: Antibodies from primary humoral responses modulate the recruitment of naive B cells during secondary responses. 著者: Jeroen M J Tas / Ja-Hyun Koo / Ying-Cing Lin / Zhenfei Xie / Jon M Steichen / Abigail M Jackson / Blake M Hauser / Xuesong Wang / Christopher A Cottrell / Jonathan L Torres / John E Warner / ...著者: Jeroen M J Tas / Ja-Hyun Koo / Ying-Cing Lin / Zhenfei Xie / Jon M Steichen / Abigail M Jackson / Blake M Hauser / Xuesong Wang / Christopher A Cottrell / Jonathan L Torres / John E Warner / Kathrin H Kirsch / Stephanie R Weldon / Bettina Groschel / Bartek Nogal / Gabriel Ozorowski / Sandhya Bangaru / Nicole Phelps / Yumiko Adachi / Saman Eskandarzadeh / Michael Kubitz / Dennis R Burton / Daniel Lingwood / Aaron G Schmidt / Usha Nair / Andrew B Ward / William R Schief / Facundo D Batista / 要旨: 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. ...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.