CD62L expression marks a functionally distinct subset of memory B cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1037568 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26779600_1.fastq.gz | Fastqsanger.gz | |||
| SRR26779600_2.fastq.gz | Fastqsanger.gz | |||
| SRR26779601_1.fastq.gz | Fastqsanger.gz | |||
| SRR26779601_2.fastq.gz | Fastqsanger.gz | |||
| SRR26779602_1.fastq.gz | Fastqsanger.gz |
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Project description:The memory B cell response consists of phenotypically distinct subsets that differ in their ability to respond upon antigen re-encounter. However, the pathways regulating the development and function of memory B cell subsets are poorly understood. Here we show that CD62L and CD44 are progressively expressed on mouse memory B cells and identify transcriptionally and functionally distinct memory B cell subsets. Bcl6 is important in regulating memory B cell subset differentiation with overexpression of Bcl6 resulting in impaired CD62L+ memory B cell development. Bcl6 regulates memory B cell subset development through control of a network of genes, including Bcl2 and Zeb2. Overexpression of Zeb2 impairs the development of CD62L+ memory B cells. Importantly, CD62L is also differentially expressed on human memory B cells following SARS-CoV-2 vaccination and identifies phenotypically distinct populations. Together, these data indicate that CD62L expression marks functionally distinct memory B cell subsets.
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Project description:The memory B cell response consists of phenotypically distinct subsets that differ in their ability to respond upon antigen re-encounter. However, the pathways regulating the development and function of memory B cell subsets are poorly understood. Here, we show that CD62L and CD44 are progressively expressed on mouse memory B cells and identify transcriptionally and functionally distinct memory B cell subsets. Bcl6 is important in regulating memory B cell subset differentiation with overexpression of Bcl6 resulting in impaired CD62L+ memory B cell development. Bcl6 regulates memory B cell subset development through control of a network of genes, including Bcl2 and Zeb2. Overexpression of Zeb2 impairs the development of CD62L+ memory B cells. Importantly, CD62L is also differentially expressed on human memory B cells following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and identifies phenotypically distinct populations. Together, these data indicate that CD62L expression marks functionally distinct memory B cell subsets.
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Project description:Memory CD8+ P14 cells were generarted through adoptive transfer and infection with LCMV armstrong. Then, early memory (after 30 - 45 days) and late memory (after 8 months) cells were sort purified based on CD62L expression. Genome-wide expression profiles were captured for early and late memory cells with high and low levels on CD62L using Affymetrics arrays to show their molecular and functional differences.
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Project description:Severe acute respiratory syndrome coronavirus 2-neutralizing antibodies primarily target the spike receptor binding domain (RBD). However, B cell antigen receptors (BCRs) on RBD-binding memory B (Bmem) cells have variation in the neutralizing activities. Here, by combining single Bmem cell profiling with antibody functional assessment, we dissected the phenotype of Bmem cell harboring the potently neutralizing antibodies in coronavirus disease 2019 (COVID-19)-convalescent individuals. The neutralizing subset was marked by an elevated CD62L expression and characterized by distinct epitope preference and usage of convergent VH (variable region of immunoglobulin heavy chain) genes, accounting for the neutralizing activities. Concordantly, the correlation was observed between neutralizing antibody titers in blood and CD62L+ subset, despite the equivalent RBD binding of CD62L+ and CD62L- subset. Furthermore, the kinetics of CD62L+ subset differed between the patients who recovered from different COVID-19 severities. Our Bmem cell profiling reveals the unique phenotype of Bmem cell subset that harbors potently neutralizing BCRs, advancing our understanding of humoral protection.
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Project description:Human Natural Killer (NK) cells comprise two main subsets, CD56bright and CD56dim cells, that differ in function, phenotype and tissue localization. To further dissect the heterogeneity of CD56dim cells, we have performed transcriptome analysis and functional ex vivo characterization of human NK cell subsets according to the expression of markers related to differentiation, migration or competence. Here, we show for the first time that the ability to respond to cytokines or to activating receptors is mutually exclusive in almost all NK cells with the exception of CD56dim CD62L+ cells. Indeed, only these cells combine the ability to produce interferon (IFN)-gamma after cytokines and proliferate in vivo during viral infection with the capacity to kill and produce cytokines upon engagement of activating receptors. Therefore, CD56dim CD62L+ cells represent a unique subset of polyfunctional NK cells. Ex vivo analysis of their function, phenotype, telomere length, frequencies during ageing as well as transfer experiments of NK cell subsets into immunodeficient mice suggest that CD56dim CD62L+ cells represent an intermediate stage of NK cell maturation, which after restimulation can accomplish multiple tasks and further develop into terminally differentiated effectors. Gene expression profiles of FACSAria sorted CD3- CD56bright CD62L+, CD3- CD56dim CD62L+ and CD3- CD56dim CD62L- NK cells from human peripheral blood of three donors were compared using Affymetrix GeneChip Human Genome HG-U133_Plus_2. After total RNA extraction, reverse transcription, cDNA extraction, the biotinylated cRNA was transcribed, fragmented, and 15 µg cRNA hybridized in triplicates for each of the three groups to the GeneChip arrays. Group1: CD3- CD56bright CD62L+,.Group2: CD3- CD56dim CD62L+, Group3: CD3- CD56dim CD62L-. Lists of differentially regulated genes were created using High Performance Chip Data Analysis (HPCDA) with Bioretis database (http://www.bioretis-analysis.de). Worldwide data sharing is possible via Bioretis, please ask the authors.
2010-05-28 | E-GEOD-21774 | biostudies-arrayexpress
Project description:Human Natural Killer (NK) cells comprise two main subsets, CD56bright and CD56dim cells, that differ in function, phenotype and tissue localization. To further dissect the heterogeneity of CD56dim cells, we have performed transcriptome analysis and functional ex vivo characterization of human NK cell subsets according to the expression of markers related to differentiation, migration or competence. Here, we show for the first time that the ability to respond to cytokines or to activating receptors is mutually exclusive in almost all NK cells with the exception of CD56dim CD62L+ cells. Indeed, only these cells combine the ability to produce interferon (IFN)-gamma after cytokines and proliferate in vivo during viral infection with the capacity to kill and produce cytokines upon engagement of activating receptors. Therefore, CD56dim CD62L+ cells represent a unique subset of polyfunctional NK cells. Ex vivo analysis of their function, phenotype, telomere length, frequencies during ageing as well as transfer experiments of NK cell subsets into immunodeficient mice suggest that CD56dim CD62L+ cells represent an intermediate stage of NK cell maturation, which after restimulation can accomplish multiple tasks and further develop into terminally differentiated effectors.
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Project description:T follicular helper (Tfh) cells, essential for germinal center reactions, are not identical, with different phenotypes reported. Whether, when and how they generate memory cells are still poorly understood. Here, through single-cell RNA-sequencing analysis of CXCR5+Bcl6+ Tfh cells generated under different conditions, we discovered, in addition to PD-1hi effector Tfh cells, a CD62L+PD1low subpopulation. CD62L-expressing Tfh cells developed independently from PD-1+ cells, and not in direct contact with B cells. More importantly, CD62L+ Tfh cells expressed memory- and stemness-associated genes; with more superior long-term survival, they readily generated PD-1hi cells in the recall response. Finally, KLF2 and IL7R, also highly expressed by CD62L+ Tfh cells, were required to regulate their development. Our work thus demonstrates a novel Tfh memory-like cell subpopulation, which may benefit our understanding on immune responses and diseases.
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Project description:Naïve CD44-lo/CD62L-hi/CD8+ T cells from C3H.SW mice were compared to CD44-hi/CD82L-lo/CD8+ effector memory T cells and CD44-lo/CD62L-hi/CD8+ postmitotic T cells, using 3 biological replicates of each type of sample. The later two cells types were highly purified at day 14 after transplantation from GVHD B6/SJL mice receiving donor C3H.SW mouse-derived naive CD44-lo/CD62L-hi/CD8+ T cells and T cell-depleted bone marrow. Recipient mice had first been lethally irradiated at a dose of 10Gy in two fractions. This is a MHC-identical minor histocompatibility antigen-mismatched mouse GVHD model of human allogeneic hematopoietic stem cell transplantation. Naive T cell samples were from pools of 2 mice each, while effector memory and postmitotic T cell samples were purified from pools of T cells from 4 mice each. After RNA extraction and cleanup, biotin labeled cRNA was prepared from 600 ng total RNA, using two rounds of in vitro transcription, and hybridized to Affymetrix Mouse Genome 430A 2.0 arrays using standard techniques. Keywords: Cell type comparison 9 samples were analyzed on 9 Affymetrix microarrays to assay mRNA levels. There were 3 biological replicates of each of 3 different cell types.
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