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Antibodies from primary humoral responses modulate the recruitment of naive B cells during secondary responses.
Tas, Jeroen M J; Koo, Ja-Hyun; Lin, Ying-Cing; Xie, Zhenfei; Steichen, Jon M; Jackson, Abigail M; Hauser, Blake M; Wang, Xuesong; Cottrell, Christopher A; Torres, Jonathan L; Warner, John E; Kirsch, Kathrin H; Weldon, Stephanie R; Groschel, Bettina; Nogal, Bartek; Ozorowski, Gabriel; Bangaru, Sandhya; Phelps, Nicole; Adachi, Yumiko; Eskandarzadeh, Saman; Kubitz, Michael; Burton, Dennis R; Lingwood, Daniel; Schmidt, Aaron G; Nair, Usha; Ward, Andrew B; Schief, William R; Batista, Facundo D.
  • Tas JMJ; The Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA 02139, USA.
  • Koo JH; The Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA 02139, USA.
  • Lin YC; The Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA 02139, USA.
  • Xie Z; The Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA 02139, USA.
  • Steichen JM; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, San
  • Jackson AM; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; Department of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA.
  • Hauser BM; The Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA 02139, USA.
  • Wang X; The Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA 02139, USA.
  • Cottrell CA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, San
  • Torres JL; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; Department of Integrative, Structural and Computational Biology, The Scripps Research In
  • Warner JE; The Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA 02139, USA.
  • Kirsch KH; The Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA 02139, USA.
  • Weldon SR; The Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA 02139, USA.
  • Groschel B; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, San
  • Nogal B; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; Department of Integrative, Structural and Computational Biology, The Scripps Research In
  • Ozorowski G; Department of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA.
  • Bangaru S; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; Department of Integrative, Structural and Computational Biology, The Scripps Research In
  • Phelps N; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, San
  • Adachi Y; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, San
  • Eskandarzadeh S; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, San
  • Kubitz M; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, San
  • Burton DR; The Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA 02139, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; Cen
  • Lingwood D; The Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA 02139, USA.
  • Schmidt AG; The Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA 02139, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
  • Nair U; The Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA 02139, USA.
  • Ward AB; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; Department of Integrative, Structural and Computational Biology, The Scripps Research In
  • Schief WR; The Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA 02139, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, San Diego, CA 92037, USA; Cen
  • Batista FD; The Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA 02139, USA; Department of Immunology, Harvard Medical School, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: fbatista1@mgh.harvard.edu.
Immunity ; 55(10): 1856-1871.e6, 2022 10 11.
Article in English | MEDLINE | ID: covidwho-2000465
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: B-Lymphocytes / Germinal Center Topics: Vaccines Limits: Animals Language: English Journal: Immunity Journal subject: Allergy and Immunology Year: 2022 Document Type: Article Affiliation country: J.immuni.2022.07.020

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Full text: Available Collection: International databases Database: MEDLINE Main subject: B-Lymphocytes / Germinal Center Topics: Vaccines Limits: Animals Language: English Journal: Immunity Journal subject: Allergy and Immunology Year: 2022 Document Type: Article Affiliation country: J.immuni.2022.07.020