Understanding Pathogenic And Physiological T Follicular Helper Cell Formation
Download Understanding Pathogenic And Physiological T Follicular Helper Cell Formation PDF/ePub or read online books in Mobi eBooks. Click Download or Read Online button to get Understanding Pathogenic And Physiological T Follicular Helper Cell Formation book now. This website allows unlimited access to, at the time of writing, more than 1.5 million titles, including hundreds of thousands of titles in various foreign languages.
Understanding Pathogenic and Physiological T Follicular Helper Cell Formation
T follicular helper (Tfh) cells localize to follicles where they provide growth and selection signals to mutated germinal center (GC) B cells, thus promoting their differentiation into high affinity long-lived plasma cells and memory B cells. T-dependent B cell differentiation also occurs extrafollicularly, giving rise to unmutated plasma cells that are important for early protection against microbial infections. Bcl-6 expression in T cells has been shown to be essential for the formation of Tfh cells and GC B cells, but little is known about its requirement in physiological extrafollicular antibody responses. We use several mouse models in which extrafollicular plasma cells can be unequivocally distinguished from those of GC origin, combined with antigen-specific T and B cells, to show that the absence of T cell-expressed Bcl-6 significantly reduces T-dependent extrafollicular antibody responses. Bcl-6+ T cells appear at the T-B border soon after T cell priming and before GC formation, and these cells express low amounts of PD-1. Their appearance precedes that of Bcl-6+PD-1hi T cells, which are found within GC. IL-21 acts early to promote both follicular and extrafollicular antibody responses. In conclusion, Bcl6+ T cells are necessary at B cell priming in order to form extrafollicular antibody responses, and these pre-GC Tfh cells can be distinguished phenotypically from GC Tfh cells. Overactivity of the GC pathway due to accumulation of Tfh cells causes autoimmunity, underscoring the need to understand the factors that control Tfh homeostasis. Here, we have identified posttranscriptional repression of interferon-gamma (Ifng) mRNA as a novel mechanism to limit Tfh cell formation. Using the sanroque lupus model, we have shown that decreased Ifng mRNA decay caused excessive interferon-gamma signaling in T cells and led to accumulation of Tfh cells, spontaneous GC, autoantibody formation and nephritis. Unlike ICOS and T-bet deficiency that failed to rescue several autoimmune manifestations, interferon-gamma receptor deficiency completely prevented lupus development. Interferon-gamma blockade after disease onset reduced Tfh cells and autoantibodies, demonstrating that interferon-gamma overproduction was required to sustain lupus-associated pathology. Increased interferon-gamma signaling caused Bcl-6 overexpression in Tfh cells and their precursors. This novel link between interferon-gamma and aberrant Tfh formation provides a rationale for interferon-gamma blockade in lupus patients with an overactive Tfh cell-associated pathway.
Fetal and Neonatal Physiology E-Book
Author: Richard Polin
language: en
Publisher: Elsevier Health Sciences
Release Date: 2021-07-29
Offering the comprehensive, authoritative information needed for effective diagnosis, treatment, and management of sick and premature infants, Fetal and Neonatal Physiology, 6th Edition, is an invaluable resource for board review, clinical rounds, scientific research, and day-to-day practice. This trusted two-volume text synthesizes recent advances in the field into definitive guidance for today's busy practitioner, focusing on the basic science needed for exam preparation and key information required for full-time practice. It stands alone as the most complete text available in this complex and fast-changing field, yet is easy to use for everyday application. - Offers definitive guidance on how to effectively manage the many health problems seen in newborn and premature infants. - Contains new chapters on Pathophysiology of Genetic Neonatal Disease, Genetic Variants and Neonatal Disease, and Developmental Biology of Lung Stem Cells, as well as significantly revised chapters on Cellular Mechanisms of Neonatal Brain Injury, Neuroprotective Therapeutic Hypothermia, Enteric Nervous System Development and Gastrointestinal Motility, and Physiology of Twin-Twin Transfusion. - Features 1,000 full-color diagrams, graphs and anatomic illustrations, 170+ chapters, and more than 350 global contributors. - Includes chapters devoted to clinical correlation that help explain the implications of fetal and neonatal physiology, as well as clinical applications boxes throughout. - Provides summary boxes at the end of each chapter and extensive cross-referencing between chapters for quick reference and review. - Allows you to apply the latest insights on genetic therapy, intrauterine infections, brain protection and neuroimaging, and much more.
HIV-Induced Damage of B Cells and Production of HIV Neutralizing Antibodies
Author: Francesca Chiodi
language: en
Publisher: Frontiers Media SA
Release Date: 2018-03-27
Multiple dysfunctions take place in the B cell compartment during HIV-1 infection, comprising depletion of resting memory B cells carrying serological memory to vaccines and previously met pathogens. In addition, population of B cells characterized by the expression of exhaustion markers are enlarged during HIV-1 infection. Antibodies with the capacity to neutralize a broad range of HIV-1 isolates can be detected only in a minority of infected patients, after a year or more from acute infection. An open question is whether the inability of producing neutralizing HIV-1 antibodies is somehow linked to the B cell immunopathology observed in patients. In this research topic we invited scientists to summarize the current state of knowledge on regulation and development of B cells and antibody responses during HIV-1 infection; fifteen contributions were received comprising both reviews and original articles. The articles are related to B cell dysfunctions identified in HIV-1 infected individuals, production of different types of antibodies (neutralizing versus non neutralizing, and of different isotypes) in vivo during HIV-1 infection and the biological factors which may impact on this process, clinical potential and applications of anti-HIV antibodies and how to achieve neutralizing antibody responses to HIV-1 epitopes upon vaccination. The topic has gathered articles on front-line research undertaken in the field of B cells and antibodies in HIV-1 infection. It is our hope that the collection of articles presented in this book may be useful for new and experienced scholars in the field and add a piece to the complex puzzle of knowledge needed for the development of an HIV-1 vaccine.