Precursor Frequency and Affinity Determine B Cell Competitive Fitness in Germinal Centers, Tested with Germline-Targeting HIV Vaccine Immunogens.
Immunity
; 48(1): 133-146.e6, 2018 01 16.
Article
em En
| MEDLINE
| ID: mdl-29287996
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
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HIV-1
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Vacinas contra a AIDS
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Centro Germinativo
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Anticorpos Monoclonais
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos