B cell expression of the enzyme PexRAP, an intermediary in ether lipid biosynthesis, promotes antibody responses and germinal center size

Published: Jan. 15, 2025

The qualities of antibody (Ab) responses provided by B lymphocytes and their plasma cell (PC) descendants are crucial facets to vaccines microbes. Metabolic processes products regulate aspects proliferation differentiation into germinal center (GC) PC states as well Ab diversification. However, there is little information about lymphoid cell-intrinsic functions enzymes that mediate ether lipid biosynthesis, including a major class membrane phospholipids. Imaging mass spectrometry (IMS) results had indicated concentrations number these phospholipids were substantially enhanced in GC compared the background average spleens. it was not clear if biosynthesis cells basis for this finding, or whether such contributes physiology responses. Ether can involve enzyme PexRAP, product Dhrs7b gene. Using combinations IMS immunization experiments mouse models with inducible loss-of-function, we now show lineage-intrinsic expression PexRAP promotes magnitude affinity maturation serological response. Moreover, data revealed -dependent increase primary follicles more prominent GC. Mechanistically, impacted via survival associated controlling levels ROS peroxidation. These findings reveal vital role peroxisomal homeostasis humoral immunity.

Language: Английский

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Simultaneous polyclonal antibody sequencing and epitope mapping by cryo electron microscopy and mass spectrometry – a perspective

Published: Jan. 16, 2025

Antibodies are a major component of adaptive immunity against invading pathogens. Here, we explore possibilities for an analytical approach to characterize the antigen-specific antibody repertoire directly from secreted proteins in convalescent serum. This aims perform simultaneous sequencing and epitope mapping using combination single particle cryo-electron microscopy (cryoEM) bottom-up proteomics techniques based on mass spectrometry (LC-MS/MS). We evaluate performance deep-learning tool ModelAngelo determining de novo sequences reconstructed 3D volumes antibody-antigen complexes. demonstrate that while map quality is critical bottleneck, it possible sequence variable domains cryoEM reconstructions with accuracies up 80-90%. While rate errors exceeds typical levels somatic hypermutation, show ModelAngelo-derived can be used assign V-genes. provides functional guide assemble peptides LC-MS/MS data more accurately improves tolerance background polyclonal sequences. Following this proof-of-principle, discuss feasibility future directions repertoires.

Language: Английский

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Simultaneous polyclonal antibody sequencing and epitope mapping by cryo electron microscopy and mass spectrometry – a perspective

Published: Jan. 16, 2025

Antibodies are a major component of adaptive immunity against invading pathogens. Here we explore possibilities for an analytical approach to characterize the antigen-specific antibody repertoire directly from secreted proteins in convalescent serum. This aims perform simultaneous sequencing and epitope mapping using combination single particle cryo-electron microscopy (cryoEM) bottom-up proteomics techniques based on mass spectrometry (LC-MS/MS). We evaluate performance deep-learning tool ModelAngelo determining de novo sequences reconstructed 3D volumes antibody-antigen complexes. demonstrate that while map quality is critical bottleneck, it possible sequence variable domains cryoEM reconstructions with accuracies up 80-90%. While rate errors exceeds typical levels somatic hypermutation, show ModelAngelo-derived can be used assign V-genes. provides functional guide assemble peptides LC-MS/MS data more accurately improves tolerance background polyclonal sequences. Following this proof-of-principle, discuss feasibility future directions repertoires.

Language: Английский

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Profile of Humoral Immunity and B Cell Pool in Infection with the SARS-CoV-2 Prototype Strain and AZD1222 (ChAdOx nCoV-19) Vaccination

Vaccines, Journal Year: 2025, Volume and Issue: 13(2), P. 101 - 101

Published: Jan. 21, 2025

Background/Objectives: Understanding the behavior of B cells during infection and vaccination is important for determining protective humoral immunity. We evaluated profile immunity cell pool in individuals who were acutely infected with SARS-CoV-2, recovered from COVID-19, or received two doses AZD1222 vaccine. Methods: Peripheral blood mononuclear (PBMCs) these subjected to vitro stimulation promote differentiation into antibody-secreting (ASCs), ELISpot abundance pan SARS-CoV-2 Spike S1-reactive IgG+ ASC. Stimulated PBMCs characterized using flow cytometry. Culture supernatants assessed soluble B-cell-activating factors. The IgA IgG S1 through ELISA. Results: displayed a robust ASC compared acute vaccinated individuals. Although frequency total subsets did not vary among groups, plasmablast increased naïve double-negative acute, recovered, Similar production appeared be present During vaccination, more produced than IgA. In patients, BAFF levels positively correlated but negatively IgA+ cells. Conclusions: Vaccination natural COVID-19 induce differential functionality suggest that new vaccines against incorporate molecular adjuvants regulate lymphocyte consider beneficial aspects response addition IgG.

Language: Английский

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DNA Nanostructures‐Based In Situ Cancer Vaccines: Mechanisms and Applications

Small Methods, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Abstract Current tumor vaccines suffer from inadequate immune responsive due to the insufficient release of antigens, low infiltration, and immunosuppressive microenvironment. DNA nanostructures with their ability precisely engineer, controlled release, biocompatibility, capability augment immunogenicity microenvironment, have gained significant attention for potential revolutionize vaccine designing. This review summarizes various applications in construction situ cancer vaccines, which can generate tumor‐associated antigens directly damaged tumors immune‐stimulation. The mechanisms components are listed, specific strategies constructing using explored underlying action elucidated. immunogenic cell death (ICD) induced by chemotherapeutic agents, photothermal therapy (PTT), photodynamic (PDT), radiation (RT) related building systematically summarized. different immunotherapy elaborated, exerts precise, long‐lasting, robust responses. current challenges future prospectives proposed. provides a holistic understanding evolving role development.

Language: Английский

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