Human anti-smallpox long-lived memory B cells are defined by dynamic interactions in the splenic niche and long-lasting germinal center imprinting
Résumé
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.
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Chappert et al-2022-Human anti-Smallpox long-lived memory B cells are defined by dynamic.pdf (9.11 Mo)
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IMMUNITY-D-22-00634_2022_Supplementals_12092022.pdf (3.62 Mo)
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Table_S1_Donors_infos_and_B_cell_profiling_v1.1.xlsx (38.87 Ko)
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Table_S2_VDJ_sequencing_and_affinity_v1.0.xlsx (485.31 Ko)
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Table_S3_single_cell_RNA_sequencing_v1.1.xlsx (637.73 Ko)
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