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Publication Abstract from PubMed

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.

Affinity gaps among B cells in germinal centers drive the selection of MPER precursors.,Ray R, Schiffner T, Wang X, Yan Y, Rantalainen K, Lee CD, Parikh S, Reyes RA, Dale GA, Lin YC, Pecetta S, Giguere S, Swanson O, Kratochvil S, Melzi E, Phung I, Madungwe L, Kalyuzhniy O, Warner J, Weldon SR, Tingle R, Lamperti E, Kirsch KH, Phelps N, Georgeson E, Adachi Y, Kubitz M, Nair U, Crotty S, Wilson IA, Schief WR, Batista FD Nat Immunol. 2024 Jun;25(6):1083-1096. doi: 10.1038/s41590-024-01844-7. Epub 2024 , May 30. PMID:38816616^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.