-
Biomedical Journal 2013Activation-induced deaminase (AID), a member of the AID/apolipoprotein B mRNA-editing enzyme-catalytic (APOBEC) family, deaminates DNA cytidines into uridines and is the... (Review)
Review
Activation-induced deaminase (AID), a member of the AID/apolipoprotein B mRNA-editing enzyme-catalytic (APOBEC) family, deaminates DNA cytidines into uridines and is the major trans-acting player of immunoglobulin (Ig) genes' diversification in mature B lymphocytes. It allows multiple antigen-driven Ig modifications through gene conversion and/or somatic hypermutation of variable region genes and also permits to switch from IgM expression to other antibody classes after class switch recombination, or to stop Ig expression after locus suicide recombination. AID is expressed at high levels into germinal center activated B cells with a very stringent temporal and spatial regulation. Despite multiple levels of regulation, off-target effects of AID are quite frequent in the B cell lineage and can affect a number of non-Ig genes, albeit at lower level than Ig genes. Beyond the immune system, AID also contributes to cytosine demethylation in undifferentiated cells by deaminating methylcytosines into thymines which are further processed by thymidine glycosylase. This contributes to the maintenance of pluripotency and to the limitation of genetic imprinting. Since AID attacks on DNA can induce replication errors, base excision repair, or mismatch repair, they are strongly mutagenic and are also driving forces of tumorigenesis, not only in B cell malignancies but also in some non-lymphoid tumors involving ectopic AID expression.
Topics: APOBEC-1 Deaminase; Animals; B-Lymphocytes; Cell Differentiation; Cytidine Deaminase; DNA Mismatch Repair; Germinal Center; Humans; Immunoglobulin Class Switching
PubMed: 24385067
DOI: 10.4103/2319-4170.113191 -
Cellular Immunology Nov 2017T-bet-expressing B cells, first identified as perpetuators of autoimmunity, were recently shown to be critical for murine antiviral responses. While their role in human... (Review)
Review
T-bet-expressing B cells, first identified as perpetuators of autoimmunity, were recently shown to be critical for murine antiviral responses. While their role in human viral infections remains unclear, B cells expressing T-bet or demonstrating a related phenotype have been described in individuals chronically infected with HIV or HCV, suggesting these cells represent a component of human antiviral responses. In this review, we discuss the induction of T-bet in B cells following both HIV and HCV infections, the factors driving T-bet B cell expansions, T-bet's relationship to atypical memory B cells, and the consequences of T-bet induction. We propose potential antiviral roles for T-bet B cells and discuss whether this population poses any utility to the HIV and HCV immune responses.
Topics: Animals; Antibodies, Viral; B-Lymphocyte Subsets; B-Lymphocytes; HIV Infections; Hepatitis C; Humans; Immunoglobulin G; Models, Immunological; T-Box Domain Proteins
PubMed: 28739077
DOI: 10.1016/j.cellimm.2017.04.012 -
Developmental and Comparative Immunology Nov 2016Mucosal surfaces are the main route of entry for pathogens in all living organisms. In the case of teleost fish, mucosal surfaces cover the vast majority of the animal.... (Review)
Review
Mucosal surfaces are the main route of entry for pathogens in all living organisms. In the case of teleost fish, mucosal surfaces cover the vast majority of the animal. As these surfaces are in constant contact with the environment, fish are perpetually exposed to a vast number of pathogens. Despite the potential prevalence and variety of pathogens, mucosal surfaces are primarily populated by commensal non-pathogenic bacteria. Indeed, a fine balance between these two populations of microorganisms is crucial for animal survival. This equilibrium, controlled by the mucosal immune system, maintains homeostasis at mucosal tissues. Teleost fish possess a diffuse mucosa-associated immune system in the intestine, with B cells being one of the main responders. Immunoglobulins produced by these lymphocytes are a critical line of defense against pathogens and also prevent the entrance of commensal bacteria into the epithelium. In this review we will summarize recent literature regarding the role of B-lymphocytes and immunoglobulins in gut immunity in teleost fish, with specific focus on immunoglobulin isotypes and the microorganisms, pathogenic and non-pathogenic that interact with the immune system.
Topics: Animals; B-Lymphocyte Subsets; B-Lymphocytes; Biological Evolution; Fish Proteins; Fishes; Homeostasis; Host-Pathogen Interactions; Immunity, Mucosal; Immunoglobulins; Infections; Intestines; Microbiota
PubMed: 26995768
DOI: 10.1016/j.dci.2016.03.013 -
Nature Communications Aug 2023During B cell maturation, transitional and mature B cells acquire cell-intrinsic features that determine their ability to exit quiescence and mount effective immune...
During B cell maturation, transitional and mature B cells acquire cell-intrinsic features that determine their ability to exit quiescence and mount effective immune responses. Here we use label-free proteomics to quantify the proteome of B cell subsets from the mouse spleen and map the differential expression of environmental sensing, transcription, and translation initiation factors that define cellular identity and function. Cross-examination of the full-length transcriptome and proteome identifies mRNAs related to B cell activation and antibody secretion that are not accompanied by detection of the encoded proteins. In addition, proteomic data further suggests that the translational repressor PDCD4 restrains B cell responses, in particular those from marginal zone B cells, to a T-cell independent antigen. In summary, our molecular characterization of B cell maturation presents a valuable resource to further explore the mechanisms underpinning the specialized functions of B cell subsets, and suggest the presence of 'poised' mRNAs that enable expedited B cell responses.
Topics: B-Lymphocytes; Proteome; Transcriptome; Animals; Mice; Cell Differentiation; Transcription Factors; RNA, Messenger; Protein Biosynthesis; B-Lymphocyte Subsets
PubMed: 37612319
DOI: 10.1038/s41467-023-40621-2 -
Current Topics in Microbiology and... 2012Early B cell factor 1 (EBF1) is a transcription factor that is critical for both B lymphopoiesis and B cell function. EBF1 is a requisite component of the B lymphocyte... (Review)
Review
Early B cell factor 1 (EBF1) is a transcription factor that is critical for both B lymphopoiesis and B cell function. EBF1 is a requisite component of the B lymphocyte transcriptional network and is essential for B lineage specification. Recent studies revealed roles for EBF1 in B cell commitment. EBF1 binds its target genes via a DNA-binding domain including a unique 'zinc knuckle', which mediates a novel mode of DNA recognition. Chromatin immunoprecipitation of EBF1 in pro-B cells defined hundreds of new, as well as previously identified, target genes. Notably, expression of the pre-B cell receptor (pre-BCR), BCR and PI3K/Akt/mTOR signaling pathways is controlled by EBF1. In this review, we highlight these current developments and explore how EBF1 functions as a tissue-specific regulator of chromatin structure at B cell-specific genes.
Topics: Animals; B-Lymphocytes; Cell Lineage; Epigenesis, Genetic; Gene Expression Regulation; Humans; Lymphopoiesis; Transcription Factors
PubMed: 21735360
DOI: 10.1007/82_2011_139 -
Viruses Mar 2022T and B cell-mediated immunity can be assessed using T cell receptor excision circle (TREC) and Kappa-deleting recombination excision circle (KREC) analysis,...
BACKGROUND
T and B cell-mediated immunity can be assessed using T cell receptor excision circle (TREC) and Kappa-deleting recombination excision circle (KREC) analysis, respectively, and successful implementation of this method requires evaluation of the correlation between the TREC frequencies and T cell subsets as well as KREC levels and B lymphocyte subsets. The aim of the present study was to evaluate the correlation between the TREC/KREC concentrations and T/B lymphocyte subsets at different stages of COVID-19.
METHODS
We examined 33 patients in the acute stage of COVID-19 (including 8 patients with poor outcomes) and 33 COVID-19 survivors. TREC/KREC concentrations were measured using quantitative real-time PCR. T/B lymphocyte subsets were determined using flow cytometry.
RESULTS
Blood TREC and KREC levels were found to be significantly lower in the acute stage of COVID-19 compared to control values. Moreover, a zero blood TREC level was a predictor of a poor disease outcome. Reductions in CD3CD4CD45ROCD62L and CD3CD8CD45ROCD62L T cell counts (as well as in the main fractions of B1 and B2 B cells) indicated a favorable outcome in COVID-19 patients in the acute stage of the disease. Decreased CD3CD4CD45ROCD62L and CD3CD8CD45ROCD62L T cell frequencies and increased CD3CD8CD45ROCD62L cell counts were found to indicate a poor outcome in patients with acute COVID-19. These patients were also found to have increased B1 cell counts while demonstrating no changes in B2 cell counts. The levels of effector T cell subsets an naïve B cells were normal in COVID-19 survivors. The most pronounced correlations between TREC/KREC levels and T/B cell subsets counts were observed in COVID-19 survivors: there were positive correlations with naïve T and B lymphocytes and negative correlations with central and effector memory T cell subsets.
CONCLUSIONS
The assessment of correlations between TREC and T cell subsets as well as KREC levels and B cell subset counts in patients with acute COVID-19 and COVID-19 survivors has shown that blood concentrations of TREC and KREC are sensitive indicators of the stage of antigen-independent differentiation of adaptive immunity cells. The results of the TREC and KREC analysis correlated with the stages of COVID-19 and differed depending on the outcome of COVID-19.
Topics: B-Lymphocyte Subsets; B-Lymphocytes; COVID-19; DNA; Humans; Receptors, Antigen, T-Cell
PubMed: 35337053
DOI: 10.3390/v14030646 -
International Journal of Molecular... Jun 2018B-lymphocyte differentiation is one of the best understood developmental pathways in the hematopoietic system. Our understanding of the developmental trajectories... (Review)
Review
B-lymphocyte differentiation is one of the best understood developmental pathways in the hematopoietic system. Our understanding of the developmental trajectories linking the multipotent hematopoietic stem cell to the mature functional B-lymphocyte is extensive as a result of efforts to identify and prospectively isolate progenitors at defined maturation stages. The identification of defined progenitor compartments has been instrumental for the resolution of the molecular features that defines given developmental stages as well as for our understanding of the mechanisms that drive the progressive maturation process. Over the last years it has become increasingly clear that the regulatory networks that control normal B-cell differentiation are targeted by mutations in human B-lineage malignancies. This generates a most interesting link between development and disease that can be explored to improve diagnosis and treatment protocols in lymphoid malignancies. The aim of this review is to provide an overview of our current understanding of molecular regulation in normal and malignant B-cell development.
Topics: Animals; B-Lymphocytes; Cell Differentiation; Humans; Leukemia, Lymphoid; Transcription Factors
PubMed: 29966360
DOI: 10.3390/ijms19071928 -
Circulation Research May 2014Insights into the important contribution of inflammation and immune functions in the development and progression of atherosclerosis have greatly improved our... (Review)
Review
Insights into the important contribution of inflammation and immune functions in the development and progression of atherosclerosis have greatly improved our understanding of this disease. Although the role of T cells has been extensively studied for decades, only recently has the role of B cells gained more attention. Recent studies have identified differential effects of different B-cell subsets and helped to clarify the still poorly understood mechanisms by which these act. B1 cells have been shown to prevent lesion formation, whereas B2 cells have been suggested to promote it. Natural IgM antibodies, mainly derived from B1 cells, have been shown to mediate atheroprotective effects, but the functional role of other immunoglobulin classes, particularly IgG, still remains elusive. In this review, we will focus on recent insights on the role of B cells and various immunoglobulin classes and how these may mediate their effects in atherosclerotic lesion formation. Moreover, we will highlight potential therapeutic approaches focusing on B-cell depletion that could be used to translate experimental evidence to human disease.
Topics: Animals; Atherosclerosis; B-Lymphocyte Subsets; B-Lymphocytes; Disease Models, Animal; Humans; Immunity, Humoral; Immunoglobulin A; Immunoglobulin E; Immunoglobulin G; Immunoglobulin M; Mice
PubMed: 24855199
DOI: 10.1161/CIRCRESAHA.113.301145 -
Arthritis Research & Therapy 2009B-cell development is tightly regulated, including the induction of B-cell memory and antibody-secreting plasmablasts and plasma cells. In the last decade, we have... (Review)
Review
B-cell development is tightly regulated, including the induction of B-cell memory and antibody-secreting plasmablasts and plasma cells. In the last decade, we have expanded our understanding of effector functions of B cells as well as their roles in human autoimmune diseases. The current review addresses the role of certain stages of B-cell development as well as plasmablasts/plasma cells in immune regulation under normal and autoimmune conditions with particular emphasis on systemic lupus erythematosus. Based on preclinical and clinical data, B cells have emerged increasingly as both effector cells as well as cells with immunoregulatory potential.
Topics: Animals; Autoimmune Diseases; Autoimmunity; B-Lymphocyte Subsets; B-Lymphocytes; Cell Differentiation; Humans; Lymphocyte Activation
PubMed: 19849820
DOI: 10.1186/ar2780 -
Proceedings of the National Academy of... Mar 2022SignificanceEpstein-Barr virus (EBV) contributes to Burkitt lymphoma and post-transplant lymphoproliferative disease (PTLD). EBV-transforming programs activate lipid...
SignificanceEpstein-Barr virus (EBV) contributes to Burkitt lymphoma and post-transplant lymphoproliferative disease (PTLD). EBV-transforming programs activate lipid metabolism to convert B cells into immortalized lymphoblastoid cell lines (LCL), a PTLD model. We found that stages of EBV transformation generate lipid reactive oxygen species (ROS) byproducts to varying degrees, and that a Burkitt-like phase of B cell outgrowth requires lipid ROS detoxification by glutathione peroxidase 4 and its cofactor glutathione. Perturbation of this redox defense in early stages of transformation or in Burkitt cells triggered ferroptosis, a programmed cell death pathway. LCLs were less dependent on this defense, a distinction tied to EBV latency programs. This highlights ferroptosis induction as a potential therapeutic approach for prevention or treatment of certain EBV+ lymphomas.
Topics: B-Lymphocytes; Burkitt Lymphoma; Cell Transformation, Viral; Ferroptosis; Herpesvirus 4, Human; Humans; Lipid Metabolism; Lymphocyte Activation; Reactive Oxygen Species; Virus Latency
PubMed: 35275790
DOI: 10.1073/pnas.2118300119