Memory B cells

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 24(1), P. 5 - 17

Published: July 3, 2023

Language: Английский

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A blueprint for tumor-infiltrating B cells across human cancers

Science, Journal Year: 2024, Volume and Issue: 384(6695)

Published: May 2, 2024

B lymphocytes are essential mediators of humoral immunity and play multiple roles in human cancer. To decode the functions tumor-infiltrating cells, we generated a cell blueprint encompassing single-cell transcriptome, cell-receptor repertoire, chromatin accessibility data across 20 different cancer types (477 samples, 269 patients). cells harbored extraordinary heterogeneity comprised 15 subsets, which could be grouped into two independent developmental paths (extrafollicular versus germinal center). Tumor extrafollicular pathway were linked with worse clinical outcomes resistance to immunotherapy. The dysfunctional program was associated glutamine-derived metabolites through epigenetic-metabolic cross-talk, promoted T cell-driven immunosuppressive program. These suggest an intratumor balance between germinal-center responses that possibly harnessed for cell-targeting

Language: Английский

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Mucosal vaccines for SARS-CoV-2: triumph of hope over experience

EBioMedicine, Journal Year: 2023, Volume and Issue: 92, P. 104585 - 104585

Published: May 3, 2023

Currently approved COVID-19 vaccines administered parenterally induce robust systemic humoral and cellular responses. While highly effective against severe disease, there is reduced effectiveness of these in preventing breakthrough infection and/or onward transmission, likely due to poor immunity elicited at the respiratory mucosa. As such, has been considerable interest developing novel mucosal that engenders more localised immune responses provide better protection recall site virus entry, contrast traditional vaccine approaches focus on immunity. In this review, we explore adaptive components immunity, evaluate epidemiological studies dissect if conferred by parenteral vaccination or drives differential efficacy acquisition discuss undergoing clinical trials assess key challenges prospects for development.

Language: Английский

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Immunological memory diversity in the human upper airway

Nature, Journal Year: 2024, Volume and Issue: 632(8025), P. 630 - 636

Published: July 31, 2024

Language: Английский

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SARS-CoV-2 immunity in animal models

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(2), P. 119 - 133

Published: Jan. 18, 2024

The COVID-19 pandemic, which was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide health crisis due to its transmissibility. SARS-CoV-2 infection results in illness and can lead significant complications affected individuals. These encompass symptoms such as coughing, distress, fever, infectious shock, distress (ARDS), even multiple-organ failure. Animal models serve crucial tools for investigating pathogenic mechanisms, immune responses, escape antiviral drug development, vaccines against SARS-CoV-2. Currently, various animal infection, nonhuman primates (NHPs), ferrets, hamsters, many different mouse models, have been developed. Each model possesses distinctive features applications. In this review, we elucidate the response elicited patients provide an overview of characteristics mainly used well corresponding responses applications these models. A comparative analysis transcriptomic alterations lungs from revealed that K18-hACE2 mouse-adapted virus exhibited highest similarity with deceased patients. Finally, highlighted current gaps related research between studies clinical investigations, underscoring lingering scientific questions demand further clarification.

Language: Английский

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B cell memory: from generation to reactivation: a multipronged defense wall against pathogens

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: March 7, 2024

Development of B cell memory is a conundrum that scientists are still exploring. Studies have been conducted in vitro and using advanced animal models to elucidate the mechanism underlying generation cells (MBCs), precise roles MBCs against pathogens, their protective functions repeated infections throughout life. Lifelong immunity invading diseases mainly result overcoming single infection. This protection largely mediated by two main components memory-MBCs long-lived plasma (PCs). The chemical cellular mechanisms encourage fat selection for or PCs an area active research. Despite fact nearly all available vaccinations rely on capacity elicit B-cell memory, we yet develop successful vaccines can induce broad-scale some deadliest diseases, including malaria AIDS. A deeper understanding specific molecular pathways govern generation, function, reactivation critical challenges associated with vaccine development. Here, reviewed literature development reactivation, interaction other types, strategies function life discussed recent advances regarding key signals transcription factors which regulate relevance quest

Language: Английский

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Cold-blooded vertebrates evolved organized germinal center–like structures

Science Immunology, Journal Year: 2023, Volume and Issue: 8(90)

Published: Nov. 1, 2023

Germinal centers (GCs) or analogous secondary lymphoid microstructures (SLMs) are thought to have evolved in endothermic species. However, living representatives of their ectothermic ancestors can mount potent antibody responses upon infection immunization, despite the apparent lack SLMs these cold-blooded vertebrates. How and where adaptive immune induced species absence GCs remain poorly understood. Here, we infected a teleost fish (trout) with parasite Ichthyophthirius multifiliis (Ich) identified formation large aggregates highly proliferating IgM + B cells CD4 T cells, contiguous splenic melanomacrophage (MMCs). Most MMC-associated (M-LAs) contained numerous antigen (Ag)–specific cells. Analysis heavy chain CDR3 repertoire microdissected M-LAs non–M-LA areas revealed that most frequent cell clones after Ich were shared only within animals. These represented polyclonal which Ag-specific clonal expansion occurred. M-LA–associated expressed high levels activation-induced cytidine deaminase underwent significant apoptosis, somatic hypermutation Igμ genes occurred prevalently Our findings demonstrate ectotherms organized GC-like roles. Moreover, our results also point primordially conserved mechanisms by mammalian develop function.

Language: Английский

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Antibody modulation of B cell responses—Incorporating positive and negative feedback

Immunity, Journal Year: 2024, Volume and Issue: 57(7), P. 1466 - 1481

Published: July 1, 2024

Language: Английский

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Notch2 controls developmental fate choices between germinal center and marginal zone B cells upon immunization

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 4, 2024

Abstract Sustained Notch2 signals induce trans-differentiation of Follicular B (FoB) cells into Marginal Zone (MZB) in mice, but the physiology underlying this differentiation pathway is still elusive. Here, we demonstrate that most receive a basal Notch signal, which intensified pre-MZB and MZB cells. Ablation or constitutive activation upon T-cell-dependent immunization reveals an interplay between antigen-induced signaling, FoB turn off signaling enter germinal centers (GC), while high leads to generation initiation plasmablast differentiation. dispensable for GC dynamics appears be re-induced some centrocytes govern expansion IgG1 + GCB Mathematical modelling suggests antigen-activated make dependent binary fate-decision differentiate either This bifurcation might serve as mechanism archive antigen-specific clones functionally spatially diverse cell states generate robust antibody memory responses.

Language: Английский

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Defective mitochondria remodelling in B cells leads to an aged immune response

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 22, 2024

Abstract The B cell response in the germinal centre (GC) reaction requires a unique bioenergetic supply. Although mitochondria are remodelled upon antigen-mediated receptor stimulation, mitochondrial function cells is still poorly understood. To gain better understanding of role function, here we generate mice with cell-specific deficiency Tfam, transcription factor necessary for biogenesis. Tfam conditional knock-out (KO) display blockage GC and bias differentiation towards memory aged-related cells, hallmarks an aged immune response. Unexpectedly, blocked KO not caused by defects supply but associated defect remodelling lysosomal compartment cells. Our results may thus describe lysosome regulation downstream antigen presentation during reaction, dysruption which manifested as

Language: Английский

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