Memory B cells

Nature reviews. Immunology, Год журнала: 2023, Номер 24(1), С. 5 - 17

Опубликована: Июль 3, 2023

Язык: Английский

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Molecular fate-mapping of serum antibody responses to repeat immunization

Nature, Год журнала: 2023, Номер 615(7952), С. 482 - 489

Опубликована: Янв. 16, 2023

Язык: Английский

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Antibody feedback regulates immune memory after SARS-CoV-2 mRNA vaccination

Nature, Год журнала: 2022, Номер 613(7945), С. 735 - 742

Опубликована: Дек. 6, 2022

Abstract Feedback inhibition of humoral immunity by antibodies was first documented in 1909 1 . Subsequent studies showed that, depending on the context, can enhance or inhibit immune responses 2,3 However, little is known about how pre-existing influence development memory B cells. Here we examined cell response individuals who received two high-affinity anti-SARS-CoV-2 monoclonal and subsequently doses an mRNA vaccine 4–8 We found that recipients produced antigen-binding neutralizing titres were only fractionally lower compared than control individuals. cells differed from those they predominantly expressed low-affinity IgM carried small numbers somatic mutations altered receptor binding domain (RBD) target specificity, consistent with epitope masking. Moreover, out 77 anti-RBD tested neutralized virus. The mechanism underlying these findings experiments mice germinal centres formed presence same dominated Our results indicate bias centre selection through distinct mechanisms: (1) lowering activation threshold for cells, thereby permitting abundant lower-affinity clones to participate response; (2) direct masking their cognate epitopes. This may part explain shifting profile elicited booster vaccinations 9

Язык: Английский

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A guide to adaptive immune memory

Nature reviews. Immunology, Год журнала: 2024, Номер unknown

Опубликована: Июнь 3, 2024

Язык: Английский

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Immunological imprinting shapes the specificity of human antibody responses against SARS-CoV-2 variants

Immunity, Год журнала: 2024, Номер 57(4), С. 912 - 925.e4

Опубликована: Март 14, 2024

Язык: Английский

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Opposing effects of pre-existing antibody and memory T cell help on the dynamics of recall germinal centers

Immunity, Год журнала: 2024, Номер 57(7), С. 1618 - 1628.e4

Опубликована: Июнь 5, 2024

Язык: Английский

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mRNA-LNP HIV-1 trimer boosters elicit precursors to broad neutralizing antibodies

Science, Год журнала: 2024, Номер 384(6697)

Опубликована: Май 16, 2024

Germline-targeting (GT) HIV vaccine strategies are predicated on deriving broadly neutralizing antibodies (bnAbs) through multiple boost immunogens. However, as the recruitment of memory B cells (MBCs) to germinal centers (GCs) is inefficient and may be derailed by serum antibody–induced epitope masking, driving further cell receptor (BCR) modification in GC-experienced after boosting poses a challenge. Using humanized immunoglobulin knockin mice, we found that GT protein trimer immunogen N332-GT5 could prime inferred-germline precursors V3-glycan–targeted bnAb BG18 primed were effectively boosted either two novel immunogens designed have minimum cross-reactivity with off-target V1-binding responses. The delivery messenger RNA lipid nanoparticles (mRNA-LNPs) generated long-lasting GCs, somatic hypermutation, affinity maturation an effective tool development.

Язык: Английский

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Designed mosaic nanoparticles enhance cross-reactive immune responses in mice

Cell, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Nanoparticle vaccines displaying combinations of SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) could protect against SARS-CoV-2 variants and spillover zoonotic sarbecoviruses into humans. Using a computational approach, we designed RBDs selected 7 natural sarbecovirus RBDs, each predicted to fold properly abrogate antibody responses variable epitopes. were attached 60-mer nanoparticles make immunogens two (mosaic-2COMs), five (mosaic-5COM), or seven (mosaic-7COM) different for comparisons with mosaic-8b, which elicited cross-reactive antibodies protected animals from challenges. Naive COVID-19 pre-vaccinated mice immunized mosaic-7COM targeting conserved RBD epitopes, their sera exhibited higher binding neutralization titers than mosaic-8b. Mosaic-2COMs mosaic-5COM potencies some mosaic-7COM. However, more potent highly mutated Omicrons, supporting its use sarbecoviruses.

Язык: Английский

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Continuous germinal center invasion contributes to the diversity of the immune response

Cell, Год журнала: 2022, Номер 186(1), С. 147 - 161.e15

Опубликована: Дек. 23, 2022

Antibody responses are characterized by increasing affinity and diversity over time. Affinity maturation occurs in germinal centers a mechanism that involves repeated cycles of somatic mutation selection. How antibody diversify while also undergoing is not as well understood. Here, we examined center (GC) dynamics tracking B cell entry, division, mutation, specificity. Our experiments show naive cells continuously enter GCs where they compete for T help undergo clonal expansion. Consistent with late invaders carry fewer mutations but can contribute up to 30% or more the late-stage centers. Notably, entering at later stages reaction immune response expressing receptors low immunogen. Paradoxically, threshold GC entry lowered presence high-affinity antibodies.

Язык: Английский

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Clonal replacement sustains long-lived germinal centers primed by respiratory viruses

Cell, Год журнала: 2022, Номер 186(1), С. 131 - 146.e13

Опубликована: Дек. 23, 2022

Язык: Английский

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