Download or read book Epigenetics of B Cells and Antibody Responses written by Paolo Casali and published by Frontiers Media SA. This book was released on 2016-04-12 with total page 123 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epigenetics is the study of changes in gene activity that are heritable but not caused by changes in the DNA sequence. By modulating gene activities, epigenetic changes regulate cell functions. They include DNA methylation, histone posttranslational modifications and gene silencing by the action of non-coding RNAs, particularly microRNAs. It is now clear that epigenetic changes regulate B cell development. By acting in concert with networks of transcription factors, they modulate the activation of B cell lineage specific gene programs and repress inappropriate gene transcription in particular B cell differentiation states.
A hallmark of B cell development in the bone marrow is the assembly of the B cell receptor (BCR) for antigen through rearrangement of immunoglobulin heavy (IgH) and light (IgL) chain V(D)J genes, as mediated by RAG1/RAG2 recombinases. Ig V(D)J rearrangement critically times the progression from pro-B cell to pre-B cell and, finally, mature B cell. Such progression is modulated by epigenetic marks, such as DNA methylation and histone posttranslational modifications, that increase chromatin accessibility and target RAG/RAG2 to V, D and J DNA. It is also dependent on the expression of multiple microRNAs. Mice deficient in Ago2, which is essential for microRNA biogenesis and function, have B cell development blocked at the pro-B cell stage. In agreement with this, B cell specific ablation of microRNA by B cell-specific knockout of Dicer virtually blocks B cell differentiation at the pro-B to pre-B cell transition.
After mature B cells encounter antigen, changes of the epigenetic landscape are induced by the same stimuli that drive the antibody response; such epigenetic changes underpin the maturation of the antibody response itself. They instruct those B cell differentiation processes, somatic hypermutation (SHM), class switch DNA recombination (CSR) and plasma cell differentiation, that are central to the maturation of the antibody response as well as differentiation of memory B cells. Inducible histone modifications, together with DNA methylation and microRNAs modulate the transcriptome, particularly the expression of activation-induced cytidine deaminase (AID), central to SHM and CSR, and B lymphocyte-induced maturation protein-1 (Blimp-1), which is central to plasma cell differentiation.
Combinatorial histone modifications also function as histone codes in the targeting of the CSR and, possibly, the SHM machinery to the Ig locus by recruiting specific adaptors (histone code readers) that can in turn target and/or stabilize CSR/SHM factors. Epigenetic alterations in memory B cells contribute to their functionally distinction from their naive counterparts. Memory B cells inherit epigenetic information from their precursors and acquire new epigenetic marks, which make these resting B cells poised to promptly respond to antigen. The cross/feedback regulation of different epigenetic modifications/elements further increases the complexity of the B cell epigenome, which interacts with the genetic information for precise modulation of gene expression. It is increasingly evident that epigenetic dysregulation in B cells, including aberrant expression of microRNAs, can result in aberrant antibody responses to microbial pathogens, emergence of pathogenic autoantibodies or B cell neoplastic transformation. Epigenetic marks are potential targets for new therapeutics in autoimmunity and B cell malignancy.
Download or read book Molecular Biology of B Cells written by Tasuku Honjo and published by Elsevier. This book was released on 2014-10-09 with total page 587 pages. Available in PDF, EPUB and Kindle. Book excerpt: Molecular Biology of B Cells, Second Edition is a comprehensive reference to how B cells are generated, selected, activated and engaged in antibody production. All of these developmental and stimulatory processes are described in molecular, immunological, and genetic terms to give a clear understanding of complex phenotypes. Molecular Biology of B Cells, Second Edition offers an integrated view of all aspects of B cells to produce a normal immune response as a constant, and the molecular basis of numerous diseases due to B cell abnormality. The new edition continues its success with updated research on microRNAs in B cell development and immunity, new developments in understanding lymphoma biology, and therapeutic targeting of B cells for clinical application. With updated research and continued comprehensive coverage of all aspects of B cell biology, Molecular Biology of B Cells, Second Edition is the definitive resource, vital for researchers across molecular biology, immunology and genetics. Covers signaling mechanisms regulating B cell differentiation Provides information on the development of therapeutics using monoclonal antibodies and clinical application of Ab Contains studies on B cell tumors from various stages of B lymphocytes Offers an integrated view of all aspects of B cells to produce a normal immune response
Download or read book Early Divergent B Cell Differentiation During Antibody Responses written by and published by . This book was released on with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The early B cell response to antigen is analyzed, probing the mechanisms of divergent differentiation into plasmablasts or germinal centre (GC) B cells. Heterozygous QMxB6 mice, in which 5% of B cells are specific for the hapten 4-hydroxy-3-nitrophenol (NP), were immunized with NP-Ficoll. Varying the antigen dose altered the proportion of B cells that entered the extra follicular or GC responses and the amount of class switch recombination (CSR). The expression of phenotypic markers and switched antibody protein in parallel with gene array analysis and single cell real time RT-PCR in responding B cells was used to identify GC and plasmablast precursors and when and where CSR occurred. The results suggest CSR occurs in B blasts before GC B cells or plasmablasts emerge in both thymus dependent and thymus independent type II responses. The protein IRF4, which is essential for CSR and plasmablast differentiation, is expressed in all responding cells immediately after immunization and selectively upregulated to high levels in plasmablasts. A hierarchy of gene expression was identified as B cells differentiate into plasmablasts whereby high IRF4 mRNA expression precedes CD138 protein, which in turn precedes Blimp1 expression.
Download or read book Regulation of the Antibody Response by Transcription Factors Scaffold Proteins and MicroRNAs written by Clayton Alexander White and published by . This book was released on 2013 with total page 183 pages. Available in PDF, EPUB and Kindle. Book excerpt: Immunoglobulin somatic hypermutation (SHM), class switch DNA recombination (CSR) and plasma cell differentiation are critical for the maturation of antibody responses to foreign and self-antigens. These processes are coordinated by a complex interplay of genetic programs, macromolecular assemblies of proteins and epigenetics. When dysregulated, these powerful processes can manifest in autoimmunity and cancer. By careful analysis of genetic knockouts, I have discovered a novel role for the Rev1 translesion DNA synthesis polymerase as a scaffold protein in the process of CSR, whereby it recruits another critical component, Ung, to switch regions through the Rev1 non-catalytic domain. Building upon previous work in the lab, I analyzed the contribution of the transcription factor HoxC4, which we had previously found regulates AID expression, to disease in lupus-prone MRL/Faslpr/lpr mice. I found that in both lupus patients and lupus-prone MRL/Faslpr/lpr mice, there is significant upregulation of AID and HoxC4. I demonstrated that HoxC4 deficiency reduced AID expression, impaired CSR, decreased serum anti-dsDNA autoantibodies and significantly reduced interchromosomal translocations, which are a source of cancer in these mice. The emerging knowledge of the importance of epigenetics in the development and function of the immune response, as well as in disease, caused me to screen epigenetic compounds for their involvement in antibody responses. I found that histone deacetylase inhibitors were potent inhibitors of the antibody and autoantibody responses in normal C57BL/6 mice and MRL/Faslpr/lpr mice. I discovered a mechanism by which HDIs directly upregulate microRNAs that target key genes of the antibody response in B cells to inhibit CSR, SHM and plasma cell differentiation. This treatment resulted in amelioration of disease and extension of lifespan in lupus-prone mice. Further, these inhibitors demonstrated similar effects on human B cells, suggesting that they may be useful in treating human disease. My studies shed light on the multiple levels of regulation that control the antibody response and demonstrate a viable class of therapeutic candidates for treating diseases that result from aberrant antibody responses.
Download or read book Epigenetics in Human Disease written by Trygve Tollefsbol and published by Academic Press. This book was released on 2018-05-18 with total page 1110 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epigenetics in Human Disease, Second Edition examines the diseases and conditions on which we have advanced knowledge of epigenetic mechanisms, such as cancer, autoimmune disorders, aging, metabolic disorders, neurobiological disorders and cardiovascular disease. In addition to detailing the role of epigenetics in the etiology, progression, diagnosis and prognosis of these diseases, novel epigenetic approaches to treatment are also explored. Fully revised and up-to-date, this new edition discusses topics of current interest in epigenetic research, including stem cell epigenetic therapy, bioinformatic analysis of NGS data, and epigenetic mechanisms of imprinting disorders. Further sections explore online epigenetic tools and datasets, early-life programming of epigenetics in age-related diseases, the epigenetics of addiction and suicide, and epigenetic approaches to regulating and preventing diabetes, cardiac disease, allergic disorders, Alzheimer’s disease, respiratory diseases, and many other human maladies. Includes contributions from leading international investigators involved in translational epigenetic research and therapeutic applications Integrates methods and applications with fundamental chapters on epigenetics in human disease, along with an evaluation of recent clinical breakthroughs Presents side-by-side coverage of the basis of epigenetic diseases and treatment pathways Provides a fully revised resource covering current developments, including stem cell epigenetic therapy, the bioinformatic analysis of NGS data, epigenetic mechanisms of imprinting disorders, online epigenetic tools and datasets, and more
Download or read book Epigenetics and Anticipation written by Mihai Nadin and published by Springer Nature. This book was released on 2022-09-26 with total page 232 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book helps transform the awareness of the anticipatory perspective into actionable methods for practitioners of medicine. It provides guidance for those who design new means and methods inspired by epigenetics, in particular to those who advance sustainable alternatives.
Download or read book Community series in epigenetics of the immune component of inflammation volume II written by Guan-Jun Yang and published by Frontiers Media SA. This book was released on 2023-09-08 with total page 130 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Epigenetic Biomarkers and Diagnostics written by Jose Luis Garcia-Gimenez and published by Academic Press. This book was released on 2015-12-07 with total page 698 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epigenetic Biomarkers and Diagnostics comprises 31 chapters contributed by leading active researchers in basic and clinical epigenetics. The book begins with the basis of epigenetic mechanisms and descriptions of epigenetic biomarkers that can be used in clinical diagnostics and prognostics. It goes on to discuss classical methods and next generation sequencing-based technologies to discover and analyze epigenetic biomarkers. The book concludes with an account of DNA methylation, post-translational modifications and noncoding RNAs as the most promising biomarkers for cancer (i.e. breast, lung, colon, etc.), metabolic disorders (i.e. diabetes and obesity), autoimmune diseases, infertility, allergy, infectious diseases, and neurological disorders. The book describes the challenging aspects of research in epigenetics, and current findings regarding new epigenetic elements and modifiers, providing guidance for researchers interested in the most advanced technologies and tested biomarkers to be used in the clinical diagnosis or prognosis of disease. Focuses on recent progress in several areas of epigenetics, general concepts regarding epigenetics, and the future prospects of this discipline in clinical diagnostics and prognostics Describes the importance of the quality of samples and clinical associated data, and also the ethical issues for epigenetic diagnostics Discusses the advances in epigenomics technologies, including next-generation sequencing based tools and applications Expounds on the utility of epigenetic biomarkers for diagnosis and prognosis of several diseases, highlighting the study of these biomarkers in cancer, cardiovascular and metabolic diseases, infertility, and infectious diseases Includes a special section that discusses the relevance of biobanks in the maintenance of high quality biosamples and clinical-associated data, and the relevance of the ethical aspects in epigenetic studies
Download or read book Lewin s GENES XII written by Jocelyn E. Krebs and published by Jones & Bartlett Learning. This book was released on 2017-03-02 with total page 838 pages. Available in PDF, EPUB and Kindle. Book excerpt: Now in its twelfth edition, Lewin's GENES continues to lead with new information and cutting-edge developments, covering gene structure, sequencing, organization, and expression. Leading scientists provide revisions and updates in their individual field of study offering readers current data and information on the rapidly changing subjects in molecular biology.
Download or read book Paul s Fundamental Immunology written by Martin Flajnik and published by Lippincott Williams & Wilkins. This book was released on 2022-07-19 with total page 3597 pages. Available in PDF, EPUB and Kindle. Book excerpt: Selected as a Doody's Core Title for 2022! Defining the field of immunology for 40 years, Paul’s Fundamental Immunology continues to provide detailed, authoritative, up-to-date information that uniquely bridges the gap between basic immunology and the disease process. The fully revised 8th edition maintains the excellence established by Dr. William E. Paul, who passed away in 2015, and is now under new editorial leadership of Drs. Martin F. Flajnik, Nevil J. Singh, and Steven M. Holland. It’s an ideal reference and gold standard text for graduate students, post-doctoral fellows, basic and clinical immunologists, microbiologists and infectious disease physicians, and any physician treating diseases in which immunologic mechanisms play a role.
Download or read book Epigenetics of the Immune System written by Dieter Kabelitz and published by Academic Press. This book was released on 2020-06-18 with total page 384 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epigenetics of the Immune System focuses on different aspects of epigenetics and immunology, providing readers with the fundamental mechanisms relating to epigenetics and the immune system. This book provides in-depth information on immune cells as a toolbox in deciphering systematically regulated mechanisms using "omics" and computational biology approaches. In addition, the book presents the translational importance of epigenetics and the immune system in our understanding of pathophysiology in diseases and its therapeutic applications. Provides an overview of most important immune mechanisms, the current status of epigenetics, and how both of them are brought together Presents key principles of immune mechanisms in epigenetics, presenting current findings and key principles Features in-depth chapter contributions from a wide range of international researchers and specialists in immunology, translational medicine and epigenetics Merges two very large areas, covering the unique interrelatedness of epigenetics and immunology
Download or read book Epigenetics in Allergy and Autoimmunity written by Christopher Chang and published by Springer Nature. This book was released on 2020-05-22 with total page 408 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book will address the growing roles of epigenetics in disease pathogenesis, and review the contribution of epigenetic modifications to disease onset and progression. The roles that epigenetics plays in facilitating effects of the environment on allergy and immunologic diseases will be reviewed. The book is divided into three parts – the first is an introduction to epigenetics and the methods that have been developed to study epigenetics, the second addresses epigenetics in allergic diseases and the third part will cover epigenetics in autoimmune diseases. With the rapid expansion of knowledge of how genes are regulated and how this regulation affects disease phenotypes, this book will be attractive to experienced researchers as well as those just launching an epigenetics research program. It will also be of interest to allergist, immunologists, rheumatologists and dermatologist who are engaged in clinical practice as a resource for understanding the basis for personalized and precision medicine. For example, the role that epigenetics plays in the pathogenesis in various allergic and autoimmune disorders and how this determines disease phenotypes will be covered extensively in this book. This book will thus help fill the gap in available resources on epigenetics in allergy and autoimmune diseases.
Download or read book Epigenetics of the Immune System written by Dieter Kabelitz and published by Academic Press. This book was released on 2020-06-04 with total page 386 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epigenetics of the Immune System focuses on different aspects of epigenetics and immunology, providing readers with the fundamental mechanisms relating to epigenetics and the immune system. This book provides in-depth information on immune cells as a toolbox in deciphering systematically regulated mechanisms using "omics" and computational biology approaches. In addition, the book presents the translational importance of epigenetics and the immune system in our understanding of pathophysiology in diseases and its therapeutic applications. Provides an overview of most important immune mechanisms, the current status of epigenetics, and how both of them are brought together Presents key principles of immune mechanisms in epigenetics, presenting current findings and key principles Features in-depth chapter contributions from a wide range of international researchers and specialists in immunology, translational medicine and epigenetics Merges two very large areas, covering the unique interrelatedness of epigenetics and immunology
Download or read book Tertiary Lymphoid Structures written by Marie-Caroline Dieu-Nosjean and published by Humana Press. This book was released on 2018-09-05 with total page 289 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume explores the various methods used to study tertiary lymphoid structures (TLS) in pathological situations. Pre-clinical models are also discussed in detail to show how TLS structure, development, and maintenance can be targeted and studied in vivo. The chapters in this book cover topics such as humans and mice; strategies to quantify TLS in order to use it in stained tissue sections; classifying a gene signature form fixed and paraffin-embedded tissues; and development of murine inflammatory models to help look at TLS in the context of infection or malignancy. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and thorough, Tertiary Lymphoid Structures: Methods and Protocols is a valuable resource that increases the reader’s knowledge on immune functions and how they will pave the way to future therapeutic applications.
Download or read book Molecular Biology of The Cell written by Bruce Alberts and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Medical Epigenetics written by and published by Academic Press. This book was released on 2021-08-27 with total page 972 pages. Available in PDF, EPUB and Kindle. Book excerpt: Medical Epigenetics, Second Edition provides a comprehensive analysis of epigenetics in health management, across a broad spectrum of disease categories and specialties, and with a focus on human systems, epigenetic diseases that affect these systems, and evolving modes of epigenetic-based treatment. Here, more than 40 leading researchers examine how each human system is affected by epigenetic maladies, offering an all-in-one resource on medical epigenetics not only for those directly involved with health care, but investigators in life sciences, biotech companies, graduate students, and others who are interested in applied aspects of epigenetics. Incorporating both diagnostic and prognostic epigenetic approaches, this volume also fully supports the application of epigenetics in precision medicine. This second edition of Medical Epigenetics, a volume in the Translational Epigenetics series, has been fully revised to address recent advances in disease epigenetics and role of epigenetics in precision medicine, with all-new chapters on skin cancer epigenetics, network analysis in medical epigenetics, machine learning in epigenetic diseases, and clinical trials of epigenetics drugs. Features chapters from leading researchers and clinicians dedicated to the burgeoning role of epigenetics in medical practice Covers emerging topics, including twin epigenetics, as well as epigenetics of gastrointestinal disease, muscle disorders, endocrine disorders, ocular medicine, pediatric diseases, sports medicine, noncoding RNA therapeutics, pain management and regenerative medicine Organized from system disorders to multi-system disorders that involve epigenetic aberrations Examines the role of epigenetics in precision medicine
Download or read book The role of epigenetics in infectious diseases written by Veron Ramsuran and published by Frontiers Media SA. This book was released on 2023-03-08 with total page 205 pages. Available in PDF, EPUB and Kindle. Book excerpt: