TRANSCRIPTIONAL REGULATION OF B CELL RESPONSES IN PROTECTION AND AUTOIMMUNITY. PDF Download
Are you looking for read ebook online? Search for your book and save it on your Kindle device, PC, phones or tablets. Download TRANSCRIPTIONAL REGULATION OF B CELL RESPONSES IN PROTECTION AND AUTOIMMUNITY. PDF full book. Access full book title TRANSCRIPTIONAL REGULATION OF B CELL RESPONSES IN PROTECTION AND AUTOIMMUNITY. by Adam James Fike. Download full books in PDF and EPUB format.
Author: Adam James Fike
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
Get Book Here
Book Description
Humoral immunity plays a pivotal role in both protective and autoimmune responses. Following a vaccination or pathogenic challenge, B lymphocytes respond by differentiating through germinal center (GC) or extrafollicular (EF) pathways to ultimately become antibody forming cells, which produce antibodies to protect the host. In autoimmune diseases, like systemic lupus erythematosus (SLE), these pathways become dysregulated which allows autoreactive B cells to produce antibodies against self-antigen. Thus, deciphering the transcriptional networks that regulate protective and aberrant responses in autoimmune diseases is paramount to guiding insights for new vaccines or therapeutics for autoimmune conditions. The GC is a site of B cell evolution and is the dominant source of high-affinity long lived plasma cells (LLPCs). GCs are canonically organized into two distinct niches, the dark (DZ) and light (LZ) zone. A bottle neck for the selection of high-affinity B cells within the GC is at the T cell-mediated selection stage in the light zone (LZ) of the GC. STAT3 is a transcription factor activated by several cytokines and signals critical to B cell biology and has a known role in plasma cell maturation. How STAT3 influences the GC reaction remains incompletely understood. Using numerous stage-specific and inducible B cell intrinsic systems, we determined that STAT3 is not required for the initiation or maintenance of a GC reaction, but rather is required for the zonal organization of the GC. STAT3-deficient GCs have an expansion of the LZ and reduction of the DZ. STAT3 exerts its functions independent of any effects on proliferation, cell cycle progression, DNA damage, or apoptosis. Further, we identified that STAT3 is not required for memory B cell (MBC) formation or the initial progression towards a plasma cell but is required for post-GC PC maturation. We discovered that STAT3 is activated in the LZ of the GC in a T-dependent manner, which permits STAT3 to orchestrate the transcriptional program required for LZ GC B cells to progress into DZ GC B cells. We next sought to delineate the functions of another STAT transcription factor, STAT4, in regulating SLE and Th1-mediated B cell responses. STAT4 has been suggested to be involved in autoimmune and protective B cell responses, but its exact contribution remains undefined. Further, numerous GWAS identified polymorphisms in or near the Stat4 locus in SLE patients. To examine the role of STAT4 in the regulation of B cell responses in SLE-like autoimmunity, we investigated the effects of STAT4 deficiency in three autoimmune- or lupus-prone mouse models: Fc[gamma]RIIB-/-, B6.Sle1b, and imiquimod treated B6.Sle1b.We found no significant effects of STAT4 on autoimmune B and T cell responses, and SLE-like autoimmunity. We next investigated if STAT4 deficiency impacted B cell responses to immunization or influenza viral infection. Again, we identified no significant impact on B or T cell responses in the absence of STAT4. From these results, we conclude that STAT4 is not required for autoimmune or protective B cell responses. Finally, B cell responses in SLE are heavily dependent upon Toll-like receptor 7 (TLR7) signaling. TLR7 activation results in the activation of several transcription factors, including interferon regulatory factor 7 (IRF7). IRF7 has been generally suspected to be involved in promoting autoimmunity, but its functions in various immune cells remain unexplored. We utilized mouse models of SLE autoimmunity and scRNAseq to delineate the mechanisms by which IRF7 in B cells drives autoimmune B cell differentiation into GC B cells and autoantibody producing antibody forming cells (AFC). Specifically, IRF7 regulates activated B cell differentiation into GC and antibody forming cell (AFC) pathways during an autoimmune response by controlling the metabolic and transcriptional program required for differentiation. These findings highlight the critical involvement of IRF7 as a primary driver of dysregulated B cell responses in systemic autoimmunity. Collectively, the findings presented in this body of work advance in our understanding of the transcriptional control of protective and autoimmune B cell responses.
Author: Adam James Fike
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
Get Book Here
Book Description
Humoral immunity plays a pivotal role in both protective and autoimmune responses. Following a vaccination or pathogenic challenge, B lymphocytes respond by differentiating through germinal center (GC) or extrafollicular (EF) pathways to ultimately become antibody forming cells, which produce antibodies to protect the host. In autoimmune diseases, like systemic lupus erythematosus (SLE), these pathways become dysregulated which allows autoreactive B cells to produce antibodies against self-antigen. Thus, deciphering the transcriptional networks that regulate protective and aberrant responses in autoimmune diseases is paramount to guiding insights for new vaccines or therapeutics for autoimmune conditions. The GC is a site of B cell evolution and is the dominant source of high-affinity long lived plasma cells (LLPCs). GCs are canonically organized into two distinct niches, the dark (DZ) and light (LZ) zone. A bottle neck for the selection of high-affinity B cells within the GC is at the T cell-mediated selection stage in the light zone (LZ) of the GC. STAT3 is a transcription factor activated by several cytokines and signals critical to B cell biology and has a known role in plasma cell maturation. How STAT3 influences the GC reaction remains incompletely understood. Using numerous stage-specific and inducible B cell intrinsic systems, we determined that STAT3 is not required for the initiation or maintenance of a GC reaction, but rather is required for the zonal organization of the GC. STAT3-deficient GCs have an expansion of the LZ and reduction of the DZ. STAT3 exerts its functions independent of any effects on proliferation, cell cycle progression, DNA damage, or apoptosis. Further, we identified that STAT3 is not required for memory B cell (MBC) formation or the initial progression towards a plasma cell but is required for post-GC PC maturation. We discovered that STAT3 is activated in the LZ of the GC in a T-dependent manner, which permits STAT3 to orchestrate the transcriptional program required for LZ GC B cells to progress into DZ GC B cells. We next sought to delineate the functions of another STAT transcription factor, STAT4, in regulating SLE and Th1-mediated B cell responses. STAT4 has been suggested to be involved in autoimmune and protective B cell responses, but its exact contribution remains undefined. Further, numerous GWAS identified polymorphisms in or near the Stat4 locus in SLE patients. To examine the role of STAT4 in the regulation of B cell responses in SLE-like autoimmunity, we investigated the effects of STAT4 deficiency in three autoimmune- or lupus-prone mouse models: Fc[gamma]RIIB-/-, B6.Sle1b, and imiquimod treated B6.Sle1b.We found no significant effects of STAT4 on autoimmune B and T cell responses, and SLE-like autoimmunity. We next investigated if STAT4 deficiency impacted B cell responses to immunization or influenza viral infection. Again, we identified no significant impact on B or T cell responses in the absence of STAT4. From these results, we conclude that STAT4 is not required for autoimmune or protective B cell responses. Finally, B cell responses in SLE are heavily dependent upon Toll-like receptor 7 (TLR7) signaling. TLR7 activation results in the activation of several transcription factors, including interferon regulatory factor 7 (IRF7). IRF7 has been generally suspected to be involved in promoting autoimmunity, but its functions in various immune cells remain unexplored. We utilized mouse models of SLE autoimmunity and scRNAseq to delineate the mechanisms by which IRF7 in B cells drives autoimmune B cell differentiation into GC B cells and autoantibody producing antibody forming cells (AFC). Specifically, IRF7 regulates activated B cell differentiation into GC and antibody forming cell (AFC) pathways during an autoimmune response by controlling the metabolic and transcriptional program required for differentiation. These findings highlight the critical involvement of IRF7 as a primary driver of dysregulated B cell responses in systemic autoimmunity. Collectively, the findings presented in this body of work advance in our understanding of the transcriptional control of protective and autoimmune B cell responses.
Author: Tasuku Honjo
Publisher: Academic Press
ISBN: 9780123979339
Category : Science
Languages : en
Pages : 0
Get Book Here
Book Description
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.
Author: Ji-Yang Wang
Publisher: Springer Nature
ISBN: 9811535329
Category : Medical
Languages : en
Pages : 181
Get Book Here
Book Description
This book contains twelve chapters contributed by prestigious international experts who are at the forefront of B cell research, and aims to provide a cutting-edge and comprehensive overview of all aspects of B cells, including B cell development, maturation and activation, germinal center reaction, memory and plasma cell differentiation, and antibody-mediated positive and negative regulation of humoral immune responses. There are also three chapters describing human diseases caused by B cell abnormalities, including primary antibody deficiencies, autoimmune diseases, and B cell malignancies. We hope that this book will become a standard and routine reference for both basic researchers and clinicians.
Author: David Ahmad Nemazee
Publisher: Karger Medical and Scientific Publishers
ISBN: 3805574541
Category : Medical
Languages : en
Pages : 281
Get Book Here
Book Description
B cells play a central role not only in adaptive immunity, but also in autoimmunity. To understand how B cells are normally prevented from reacting to self-tissue, what goes wrong in autoimmunity, and how B cells contribute to it is the aim of this book. This volume includes more than a dozen in-depth reviews by researchers specializing in various aspects of basic B cell biology that have relevance to autoimmune diseases. These up-to-date chapters present the latest information on B cell signal transduction, apoptosis, genetics and molecular biology. Also featured are chapters with special reference to particular autoimmune diseases in which B cells have been shown to play a critical role, such as type 1 diabetes, chronic graft-versus-host disease and lupus erythematosus. Further topics covered include the role of the complement system, rheumatoid factors, and anti-DNA autoantibodies as well as important related areas such as natural autoantibodies, B cell immune tolerance, Toll receptor signaling, and the immunobiology of BAFF/BLyS. Both basic researchers and clinician scientists who wish to understand the role of B lymphocytes in immune tolerance and autoimmunity will benefit from this timely publication.
Author: Kenneth Murphy
Publisher: Garland Science
ISBN: 9780815344575
Category : Medical
Languages : en
Pages :
Get Book Here
Book Description
The Janeway's Immunobiology CD-ROM, Immunobiology Interactive, is included with each book, and can be purchased separately. It contains animations and videos with voiceover narration, as well as the figures from the text for presentation purposes.
Author: Tomohiro Kurosaki
Publisher: Springer
ISBN: 3319261339
Category : Medical
Languages : en
Pages : 231
Get Book Here
Book Description
This volume details our current understanding of the architecture and signaling capabilities of the B cell antigen receptor (BCR) in health and disease. The first chapters review new insights into the assembly of BCR components and their organization on the cell surface. Subsequent contributions focus on the molecular interactions that connect the BCR with major intracellular signaling pathways such as Ca2+ mobilization, membrane phospholipid metabolism, nuclear translocation of NF-kB or the activation of Bruton’s Tyrosine Kinase and MAP kinases. These elements orchestrate cytoplasmic and nuclear responses as well as cytoskeleton dynamics for antigen internalization. Furthermore, a key mechanism of how B cells remember their cognate antigen is discussed in detail. Altogether, the discoveries presented provide a better understanding of B cell biology and help to explain some B cell-mediated pathogenicities, like autoimmune phenomena or the formation of B cell tumors, while also paving the way for eventually combating these diseases.
Author: Gerald J. Prud'homme
Publisher: Springer
ISBN: 9780306479915
Category : Medical
Languages : en
Pages : 149
Get Book Here
Book Description
Autoimmune diseases are diverse and responsible for considerable morbidity. Their etiology remains largely unknown, and current therapy with anti-inflammatory drugs is prone to adverse effects, and rarely curative. New therapies with anti-cytokine antibodies or receptors are promising, but require frequent administration of expensive protein drugs. Gene Therapy of Autoimmune Diseases comprehensively reviews research in gene therapy for autoimmune diseases with viral or non-viral vectors. Gene therapy offers the possibility of long-term, continuous delivery of a wide variety of immunosuppressive, anti-inflammatory, or tolerance-inducing agents. Moreover, highly specific genetically modified cells can be produced. This book discusses the most promising avenues in this exciting new field.
Author: Bruce Alberts
Publisher:
ISBN: 9780815332183
Category : Cytology
Languages : en
Pages : 0
Get Book Here
Book Description
Author: Yehuda Shoenfeld
Publisher: CRC Press
ISBN: 9780849355011
Category : Medical
Languages : en
Pages : 374
Get Book Here
Book Description
Natural Autoantibodies provides an in-depth analysis of all aspects of natural antibodies. The book examines the advantages and pitfalls of every type of technique that is widely used for detecting autoantibodies. It also covers the sequencing of human autoantibody genes, discussing how sequencing is undertaken and the genetic clues available to elucidate the genetic origins of autoimmunity. Animal models of autoimmunity are also covered, and the up-to-date account provided in this book explains how natural autoantibodies have important regulatory functions and also occasionally serve as templates for autoimmunity. Other topics examined in Natural Autoantibodies: Their Physiological Role and Regulatory Significance include idiotypes of natural autoantibodies; the pathogenic role of natural autoantibodies; and methods to measure the effects of genetic and sex hormones, as well as aging, on natural autoantibodies. The book will be an excellent research tool and reference for immunologists, rheumatologists, and others interested in the topic.
Author: P. E. Bigazzi
Publisher: CRC Press
ISBN: 9780824785505
Category : Medical
Languages : en
Pages : 328
Get Book Here
Book Description
Surveys the biotechnologically influenced advances in the understanding of systemic autoimmune disorders, highlighting recent research using cell biology and biochemistry, the cloning of immune cells, recombinant DNA, and molecular genetics. Among the topics are the role of complement in inflammatio