1. Human anti-smallpox long-lived memory B cells are defined by dynamic interactions in the splenic niche and long-lasting germinal center imprinting.
- Author
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Chappert P, Huetz F, Espinasse MA, Chatonnet F, Pannetier L, Da Silva L, Goetz C, Mégret J, Sokal A, Crickx E, Nemazanyy I, Jung V, Guerrera C, Storck S, Mahévas M, Cosma A, Revy P, Fest T, Reynaud CA, and Weill JC
- Subjects
- B-Lymphocytes metabolism, Germinal Center, Humans, Immunoglobulin G metabolism, Immunologic Memory, Memory B Cells
- Abstract
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 CD21
hi CD20hi 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., Competing Interests: Declaration of interests M.M. received research funds from GSK and personal fees from LFB and Amgen, and J.-C.W. received consulting fees from Institut Mérieux, all outside of the submitted work., (Copyright © 2022 Elsevier Inc. All rights reserved.)- Published
- 2022
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