Diverse priming outcomes under conditions of very rare precursor B cells

Rare naive B cells have special pathogen-recognition features that enable outsized contributions to protective immunity but infrequently participate in immune responses. We investigatee how germline-targeting vaccine delivery and adjuvant selection affect priming of exceptionally rare BG18-like HIV broadly neutralizing antibody-precursor B cells (<1-in-50 million) in non-human primates. Only escalating dose (ED) priming immunization using the saponin adjuvant SMNP elicited detectable BG18-like cells in germinal centers (GCs) compared with other conditions. All groups had strong GC responses, but only ED+SMNP and bolus+SMNP induced BG18-like memory B cells in >50% of animals. One group had vaccine-specific GC responses equivalent to ED+SMNP but scarce BG18-like B cells. Following homologous boosting, BG18-like memory B cells were present in a bolus priming group but with lower somatic hypermutation and affinities than ED+SMNP. This outcome inversely associated with post-prime antibody titers, suggesting antibody feedback significantly influences rare precursor B cell responses. Thus, antigen and inflammatory stimuli extensively impact priming and affinity maturation of rare B cells.

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Publication Details

Journal
Immunity
Published
2025-04-01
DOI
https://doi.org/10.1016/j.immuni.2025.03.003
Citations
9
Primary Topic
Immunodeficiency and Autoimmune Disorders
Type
article
Field-Weighted Citation Impact
7.18
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Diverse priming outcomes under conditions of very rare precursor B cells

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Diverse priming outcomes under conditions of very rare precursor B cells

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article en
9 citations

Abstract

Rare naive B cells have special pathogen-recognition features that enable outsized contributions to protective immunity but infrequently participate in immune responses. We investigatee how germline-targeting vaccine delivery and adjuvant selection affect priming of exceptionally rare BG18-like HIV broadly neutralizing antibody-precursor B cells (<1-in-50 million) in non-human primates. Only escalating dose (ED) priming immunization using the saponin adjuvant SMNP elicited detectable BG18-like cells in germinal centers (GCs) compared with other conditions. All groups had strong GC responses, but only ED+SMNP and bolus+SMNP induced BG18-like memory B cells in >50% of animals. One group had vaccine-specific GC responses equivalent to ED+SMNP but scarce BG18-like B cells. Following homologous boosting, BG18-like memory B cells were present in a bolus priming group but with lower somatic hypermutation and affinities than ED+SMNP. This outcome inversely associated with post-prime antibody titers, suggesting antibody feedback significantly influences rare precursor B cell responses. Thus, antigen and inflammatory stimuli extensively impact priming and affinity maturation of rare B cells.

ImmunityVol. 58(4)
Scripps Research Institute (US), International AIDS Vaccine Initiative (US), La Jolla Institute for Immunology (US), Emory Healthcare (US), University of Louisville (US), Emory University (US), Massachusetts Institute of Technology (US)
Zero hunger
Openalex Percentile: Top 3%
Immunodeficiency and Autoimmune Disorders
7.18
DOIOpen Access PDFOpenAlex
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