Precursor Frequency and Affinity Determine B Cell Competitive Fitness in Germinal Centers, Tested with Germline-Targeting HIV Vaccine Immunogens. Immunity 2018;48(1):133-146.e6 doi: S1074-7613(17)30524-1
Scientific Publications
- PMID: 29287996
- Title: Precursor Frequency and Affinity Determine B Cell Competitive Fitness in Germinal Centers Tested with Germline Targeting HIV Vaccine Immunogens
- 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.
- Date: 1970-08-21
- Year: 2018
- Journal: Immunity
- PMID Author: Abbott RK, Lee JH, Menis S, Skog P, Rossi M, Ota T, Kulp DW, Bhullar D, Kalyuzhniy O, Havenar-Daughton C, Schief WR, Nemazee D, Crotty S
- PMC Link #: PMC5773359
- IAVI Topics: HIV Immunogen Design
Precursor Frequency and Affinity Determine B Cell Competitive Fitness in Germinal Centers Tested with Germline Targeting HIV Vaccine Immunogens
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