Human anti-smallpox long-lived memory B cells are defined by dynamic interactions in the splenic niche and long-lasting germinal center imprinting

Chappert, Pascal; Huetz, François; Espinasse, Marie-Alix; Chatonnet, Fabrice; Pannetier, Louise; Silva, Lucie Da; Goetz, Clara; Mégret, Jérôme; Sokal, Aurélien; Crickx, Étienne; Nemazanyy, Ivan; Jung, Vincent; Guerrera, Chiara; Storck, Sébastien; Mahévas, Matthieu; Cosma, Antonio; Revy, Patrick; Fest, Thierry; Reynaud, Claude‐Agnès; Weill, Jean‐Claude

doi:10.1016/j.immuni.2022.08.019

Cited by 27 publications

(17 citation statements)

References 112 publications

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“…This study offered the unique opportunity to elucidate the longevity of MBCs as smallpox was eradicated more than 40 years ago, ensuring no re‐occurring exposure since 1980. Isolated B5 + MBCs showed an IgG + , CD21 + , CD27 + , CD73 + phenotype, but no distinct (surface) markers were identified to distinguish B5 + MBCs from the regular MBC population 2 . Moreover, B5 + MBCs carried medium‐ to high‐affinity B‐cell receptors (KD = 10 −8 to 10 −10 ) with a narrow distribution of mutations, suggesting extensive clonal selection.…”

Section: Figurementioning

confidence: 99%

“…Moreover, B5 + MBCs carried medium‐ to high‐affinity B‐cell receptors (KD = 10 −8 to 10 −10 ) with a narrow distribution of mutations, suggesting extensive clonal selection. The short window of antigen exposure may implicate prolonged antigen presentation in the spleen and/or a mechanism where exclusively high‐affinity MBCs differentiate into long‐lived MBCs 2 …”

Section: Figurementioning

confidence: 99%

“…The short window of antigen exposure may implicate prolonged antigen presentation in the spleen and/or a mechanism where exclusively high-affinity MBCs differentiate into long-lived MBCs. 2 Nonetheless, two distinct B5 + populations -distinguishable by their CD21 expression -have been identified. CD21 high CD20 high MBCs were in the spleen while CD21 CD20 int MBCs were primarily identified in the peripheral blood, suggesting that the microenvironment determine the phenotype.…”

mentioning

confidence: 99%

“…Additionally, B5 + MBCs showed similar surface expression pattern as marginal zone B cells (LFA-1, ICAM1, NOTCH and inhibitory receptors), which are re-circulating cells patrolling for antigens in the bloodstream. 1,2 This would implicate that long-lived MBCs may recirculate between spleen and peripheral blood.…”

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confidence: 99%

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Memory B cells with extraordinary longevity upon smallpox vaccination: Implications for type 1 hypersensitivities

Ehlers

2023

Allergy

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The immunological memory allows fast responding to pathogens that previously invaded the immune system. One of the key players are memory B cells (MBC). MBCs are generated upon crosstalk with antigen-specific T cells. They, subsequently, enter the light zone of the germinal center where they undergo somatic hypermutations. Upon migrating to the dark zone, high affinity clones are selected by their ability to interact with follicular dendritic and T cells. Selected clones can differentiate into MBCs residing in the spleen or peripheral blood (Figure 1). 1 To gain a better understanding of MBCs, Chappert and colleagues isolated B5 (smallpox antigen)-specific IgG + B cells from the spleen of deceased donors who received a smallpox vaccination during their lifetime. This study offered the unique opportunity to elucidate the longevity of MBCs as smallpox was eradicated more than 40 years ago, ensuring no re-occurring exposure since 1980. Isolated B5 + MBCs showed an IgG + , CD21 + , CD27 + , CD73 + phenotype, but no distinct (surface) markers were identified to distinguish B5 + MBCs from the regular MBC population. 2 Moreover, B5 + MBCs

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Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Memory B cells with extraordinary longevity upon smallpox vaccination: Implications for type 1 hypersensitivities

Ehlers

2023

Allergy

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“…The protection slowly wanes over time, leading to pauci-symptomatic infection 14,16,17 . The memory B cell response generated by smallpox vaccine is however long-lasting 18,19 . Depending on studies, up to 90% of individuals vaccinated 25-75 years ago maintain substantial humoral or cellular immunity against VACV [20][21][22] .…”

Section: Introductionmentioning

confidence: 99%

Complement-dependent mpox virus-neutralizing antibodies in infected and vaccinated individuals

Hubert

Guivel‐Benhassine

Bruel

et al. 2023

Preprint

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Mpox virus (MPXV) caused a multi-country outbreak in non-endemic areas in 2022. The Modified Vaccinia Ankara (MVA)-based vaccine was used as prophylaxis, but its effectiveness remains poorly characterized. Here, we developed two assays for quantification of neutralizing antibodies (NAbs), using MVA-GFP or a recently isolated MPXV. We measured NAb levels in 470 sera from control, MPXV-infected or MVA-vaccinated individuals. Various levels of MVA NAbs were detected after infection, historic smallpox or MVA vaccination. MPXV was barely sensitive to neutralization. Addition of complement enhanced detection of responsive individuals and NAb levels. Anti-MVA and -MPXV NAbs were observed in 94% and 82% of infected individuals, respectively, and 92% and 56% of MVA vaccinees, respectively. NAb titers were higher in individuals born before 1980, highlighting the impact of historic smallpox vaccination on humoral immunity. Altogether, our results indicate that MPXV neutralization is complement-dependent and help uncover the mechanisms underlying vaccine effectiveness.

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Memory B Cells and Plasma Cells

McGrath,

Weisel,

Radbruch

et al. 2024

Molecular Biology of B Cells

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Human anti-smallpox long-lived memory B cells are defined by dynamic interactions in the splenic niche and long-lasting germinal center imprinting

Cited by 27 publications

References 112 publications

Memory B cells with extraordinary longevity upon smallpox vaccination: Implications for type 1 hypersensitivities

Memory B cells with extraordinary longevity upon smallpox vaccination: Implications for type 1 hypersensitivities

Complement-dependent mpox virus-neutralizing antibodies in infected and vaccinated individuals

Memory B Cells and Plasma Cells

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