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B cell receptor signaling in germinal centers prolongs survival and primes B cells for selection

Germinal centers (GCs) are sites of B cell clonal expansion, diversification, and antibody affinity selection. This process is limited and directed by T follicular helper cells that provide helper signals to B cells that endocytose, process, and present cognate antigens in proportion to their B cell...

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Autores principales: Chen, Spencer T., Oliveira, Thiago Y., Gazumyan, Anna, Cipolla, Melissa, Nussenzweig, Michel C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10424567/
https://www.ncbi.nlm.nih.gov/pubmed/36882061
http://dx.doi.org/10.1016/j.immuni.2023.02.003
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author Chen, Spencer T.
Oliveira, Thiago Y.
Gazumyan, Anna
Cipolla, Melissa
Nussenzweig, Michel C.
author_facet Chen, Spencer T.
Oliveira, Thiago Y.
Gazumyan, Anna
Cipolla, Melissa
Nussenzweig, Michel C.
author_sort Chen, Spencer T.
collection PubMed
description Germinal centers (GCs) are sites of B cell clonal expansion, diversification, and antibody affinity selection. This process is limited and directed by T follicular helper cells that provide helper signals to B cells that endocytose, process, and present cognate antigens in proportion to their B cell receptor (BCR) affinity. Under this model, the BCR functions as an endocytic receptor for antigen capture. How signaling through the BCR contributes to selection is not well understood. To investigate the role of BCR signaling in GC selection, we developed a tracker for antigen binding and presentation and a Bruton’s tyrosine kinase drug-resistant-mutant mouse model. We showed that BCR signaling per se is necessary for the survival and priming of light zone B cells to receive T cell help. Our findings provide insight into how high-affinity antibodies are selected within GCs and are fundamental to our understanding of adaptive immunity and vaccine development.
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spelling pubmed-104245672023-08-14 B cell receptor signaling in germinal centers prolongs survival and primes B cells for selection Chen, Spencer T. Oliveira, Thiago Y. Gazumyan, Anna Cipolla, Melissa Nussenzweig, Michel C. Immunity Article Germinal centers (GCs) are sites of B cell clonal expansion, diversification, and antibody affinity selection. This process is limited and directed by T follicular helper cells that provide helper signals to B cells that endocytose, process, and present cognate antigens in proportion to their B cell receptor (BCR) affinity. Under this model, the BCR functions as an endocytic receptor for antigen capture. How signaling through the BCR contributes to selection is not well understood. To investigate the role of BCR signaling in GC selection, we developed a tracker for antigen binding and presentation and a Bruton’s tyrosine kinase drug-resistant-mutant mouse model. We showed that BCR signaling per se is necessary for the survival and priming of light zone B cells to receive T cell help. Our findings provide insight into how high-affinity antibodies are selected within GCs and are fundamental to our understanding of adaptive immunity and vaccine development. 2023-03-14 2023-03-06 /pmc/articles/PMC10424567/ /pubmed/36882061 http://dx.doi.org/10.1016/j.immuni.2023.02.003 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Chen, Spencer T.
Oliveira, Thiago Y.
Gazumyan, Anna
Cipolla, Melissa
Nussenzweig, Michel C.
B cell receptor signaling in germinal centers prolongs survival and primes B cells for selection
title B cell receptor signaling in germinal centers prolongs survival and primes B cells for selection
title_full B cell receptor signaling in germinal centers prolongs survival and primes B cells for selection
title_fullStr B cell receptor signaling in germinal centers prolongs survival and primes B cells for selection
title_full_unstemmed B cell receptor signaling in germinal centers prolongs survival and primes B cells for selection
title_short B cell receptor signaling in germinal centers prolongs survival and primes B cells for selection
title_sort b cell receptor signaling in germinal centers prolongs survival and primes b cells for selection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10424567/
https://www.ncbi.nlm.nih.gov/pubmed/36882061
http://dx.doi.org/10.1016/j.immuni.2023.02.003
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