TY - JOUR
T1 - Human anti-smallpox long-lived memory B cells are defined by dynamic interactions in the splenic niche and long-lasting germinal center imprinting
AU - Chappert, Pascal
AU - Huetz, François
AU - Espinasse, Marie Alix
AU - Chatonnet, Fabrice
AU - Pannetier, Louise
AU - Da Silva, Lucie
AU - Goetz, Clara
AU - Mégret, Jérome
AU - Sokal, Aurélien
AU - Crickx, Etienne
AU - Nemazanyy, Ivan
AU - Jung, Vincent
AU - Guerrera, Chiara
AU - Storck, Sébastien
AU - Mahévas, Matthieu
AU - Cosma, Antonio
AU - Revy, Patrick
AU - Fest, Thierry
AU - Reynaud, Claude Agnès
AU - Weill, Jean Claude
N1 - Funding Information:
This work was funded by the Fondation Princesse Grace , by a Mérieux grant and by ERC Advanced Grants (Memo-B and B-response). M.A.E was supported by a grant from the Fondation EDF . MetaToul is part of the national infrastructure MetaboHUB-ANR-11-INBS-0010 . P.R. is a scientist from Centre National de la Recherche Scientifique (CNRS).
Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/10/11
Y1 - 2022/10/11
N2 - Memory B cells (MBCs) can persist for a lifetime, but the mechanisms that allow their long-term survival remain poorly understood. Here, we isolated and analyzed human splenic smallpox/vaccinia protein B5-specific MBCs in individuals who were vaccinated more than 40 years ago. Only a handful of clones persisted over such an extended period, and they displayed limited intra-clonal diversity with signs of extensive affinity-based selection. These long-lived MBCs appeared enriched in a CD21hiCD20hi IgG+ splenic B cell subset displaying a marginal-zone-like NOTCH/MYC-driven signature, but they did not harbor a unique longevity-associated transcriptional or metabolic profile. Finally, the telomeres of B5-specific, long-lived MBCs were longer than those in patient-paired naive B cells in all the samples analyzed. Overall, these results imply that separate mechanisms such as early telomere elongation, affinity selection during the contraction phase, and access to a specific niche contribute to ensuring the functional longevity of MBCs.
AB - Memory B cells (MBCs) can persist for a lifetime, but the mechanisms that allow their long-term survival remain poorly understood. Here, we isolated and analyzed human splenic smallpox/vaccinia protein B5-specific MBCs in individuals who were vaccinated more than 40 years ago. Only a handful of clones persisted over such an extended period, and they displayed limited intra-clonal diversity with signs of extensive affinity-based selection. These long-lived MBCs appeared enriched in a CD21hiCD20hi IgG+ splenic B cell subset displaying a marginal-zone-like NOTCH/MYC-driven signature, but they did not harbor a unique longevity-associated transcriptional or metabolic profile. Finally, the telomeres of B5-specific, long-lived MBCs were longer than those in patient-paired naive B cells in all the samples analyzed. Overall, these results imply that separate mechanisms such as early telomere elongation, affinity selection during the contraction phase, and access to a specific niche contribute to ensuring the functional longevity of MBCs.
KW - affinity selection
KW - long-lasting immune memory
KW - memory B cells
KW - smallpox
KW - splenic microenvironment
KW - telomeres
KW - vaccinia
UR - https://www.scopus.com/pages/publications/85139285570
UR - https://pubmed.ncbi.nlm.nih.gov/36130603
U2 - 10.1016/j.immuni.2022.08.019
DO - 10.1016/j.immuni.2022.08.019
M3 - Article
C2 - 36130603
SN - 1074-7613
VL - 55
SP - 1872-1890.e9
JO - Immunity
JF - Immunity
IS - 10
ER -