Affinity gaps among B cells in germinal centers drive the selection of MPER precursors.

Autor:	Ray R; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA., Schiffner T; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA.; Institute for Drug Discovery, Leipzig University Medical Faculty, Leipzig, Germany., Wang X; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA., Yan Y; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA., Rantalainen K; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA., Lee CD; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA.; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA., Parikh S; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA., Reyes RA; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA., Dale GA; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA., Lin YC; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA., Pecetta S; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA.; Moderna, Inc., Cambridge, MA, USA., Giguere S; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA., Swanson O; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA., Kratochvil S; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA., Melzi E; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA., Phung I; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA.; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA, USA.; Department of Medicine, University of California, San Diego, La Jolla, CA, USA., Madungwe L; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA., Kalyuzhniy O; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA., Warner J; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA., Weldon SR; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA., Tingle R; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA., Lamperti E; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA., Kirsch KH; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA., Phelps N; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA., Georgeson E; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA., Adachi Y; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA., Kubitz M; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA., Nair U; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA., Crotty S; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA.; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA, USA.; Department of Medicine, University of California, San Diego, La Jolla, CA, USA., Wilson IA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA.; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA., Schief WR; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA. schief@scripps.edu.; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA. schief@scripps.edu.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA. schief@scripps.edu.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA. schief@scripps.edu.; Moderna, Inc., Cambridge, MA, USA. schief@scripps.edu., Batista FD; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA. fbatista1@mgh.harvard.edu.; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. fbatista1@mgh.harvard.edu.
Jazyk:	angličtina
Zdroj:	Nature immunology [Nat Immunol] 2024 Jun; Vol. 25 (6), pp. 1083-1096. Date of Electronic Publication: 2024 May 30.
DOI:	10.1038/s41590-024-01844-7
Abstrakt:	Current prophylactic human immunodeficiency virus 1 (HIV-1) vaccine research aims to elicit broadly neutralizing antibodies (bnAbs). Membrane-proximal external region (MPER)-targeting bnAbs, such as 10E8, provide exceptionally broad neutralization, but some are autoreactive. Here, we generated humanized B cell antigen receptor knock-in mouse models to test whether a series of germline-targeting immunogens could drive MPER-specific precursors toward bnAbs. We found that recruitment of 10E8 precursors to germinal centers (GCs) required a minimum affinity for germline-targeting immunogens, but the GC residency of MPER precursors was brief due to displacement by higher-affinity endogenous B cell competitors. Higher-affinity germline-targeting immunogens extended the GC residency of MPER precursors, but robust long-term GC residency and maturation were only observed for MPER-HuGL18, an MPER precursor clonotype able to close the affinity gap with endogenous B cell competitors in the GC. Thus, germline-targeting immunogens could induce MPER-targeting antibodies, and B cell residency in the GC may be regulated by a precursor-competitor affinity gap. (© 2024. The Author(s).)
Databáze:	MEDLINE
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