Precursor Frequency and Affinity Determine B Cell Competitive Fitness in Germinal Centers, Tested with Germline-Targeting HIV Vaccine Immunogens.

TitlePrecursor Frequency and Affinity Determine B Cell Competitive Fitness in Germinal Centers, Tested with Germline-Targeting HIV Vaccine Immunogens.
Publication TypeJournal Article
Year of Publication2018
AuthorsAbbott RK, Lee J H, Menis S, Skog P, Rossi M, Ota T, Kulp DW, Bhullar D, Kalyuzhniy O, Havenar-Daughton C, Schief WR, Nemazee D, Crotty S
JournalImmunity
Volume48
Issue1
Pagination133-146.e6
Date Published01/16/2018
ISSN1097-4180
Abstract

How precursor frequencies and antigen affinities impact interclonal B cell competition is a particularly relevant issue for candidate germline-targeting HIV vaccine designs because of the in vivo rarity of naive B cells that recognize broadly neutralizing epitopes. Knowing the frequencies and affinities of HIV-specific VRC01-class naive human B cells, we transferred B cells with germline VRC01 B cell receptors into congenic recipients to elucidate the roles of precursor frequency, antigen affinity, and avidity on B cell responses following immunization. All three factors were interdependently limiting for competitive success of VRC01-class B cells. In physiological high-affinity conditions using a multivalent immunogen, rare VRC01-class B cells successfully competed in germinal centers (GC), underwent extensive somatic hypermutation, and differentiated into memory B cells. The data reveal dominant influences of precursor frequency, affinity, and avidity for interclonal GC competition and indicate that germline-targeting immunogens can overcome these challenges with high-affinity multimeric designs.

DOI10.1016/j.immuni.2017.11.023
Alternate JournalImmunity
PubMed ID29287996
PubMed Central IDPMC5773359
Grant ListR01 AI124796 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
R01 AI073148 / AI / NIAID NIH HHS / United States
T32 AI125179 / AI / NIAID NIH HHS / United States
R01 AI128836 / AI / NIAID NIH HHS / United States
CHAVI-ID: 
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