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Immunological Reviews Sep 2010
Review
Topics: Animals; B-Lymphocytes; Humans; Immunologic Memory; Lymphocyte Activation
PubMed: 20727025
DOI: 10.1111/j.1600-065X.2010.00946.x -
Annual Review of Immunology Apr 2020The age-associated B cell subset has been the focus of increasing interest over the last decade. These cells have a unique cell surface phenotype and transcriptional... (Review)
Review
The age-associated B cell subset has been the focus of increasing interest over the last decade. These cells have a unique cell surface phenotype and transcriptional signature, and they rely on TLR7 or TLR9 signals in the context of Th1 cytokines for their formation and activation. Most are antigen-experienced memory B cells that arise during responses to microbial infections and are key to pathogen clearance and control. Their increasing prevalence with age contributes to several well-established features of immunosenescence, including reduced B cell genesis and damped immune responses. In addition, they are elevated in autoimmune and autoinflammatory diseases, and in these settings they are enriched for characteristic autoantibody specificities. Together, these features identify age-associated B cells as a subset with pivotal roles in immunological health, disease, and aging. Accordingly, a detailed understanding of their origins, functions, and physiology should make them tractable translational targets in each of these settings.
Topics: Aging; Animals; Autoimmunity; B-Lymphocyte Subsets; B-Lymphocytes; Biomarkers; Cytokines; Disease Susceptibility; Homeostasis; Humans; Immunologic Memory; Immunosenescence; Lymphocyte Activation
PubMed: 31986068
DOI: 10.1146/annurev-immunol-092419-031130 -
Blood Sep 2008The discovery that lymphocyte subpopulations participate in distinct components of the immune response focused attention onto the origins and function of lymphocytes... (Review)
Review
The discovery that lymphocyte subpopulations participate in distinct components of the immune response focused attention onto the origins and function of lymphocytes more than 40 years ago. Studies in the 1960s and 1970s demonstrated that B and T lymphocytes were responsible primarily for the basic functions of antibody production and cell-mediated immune responses, respectively. The decades that followed have witnessed a continuum of unfolding complexities in B-cell development, subsets, and function that could not have been predicted. Some of the landmark discoveries that led to our current understanding of B lymphocytes as the source of protective innate and adaptive antibodies are highlighted in this essay. The phenotypic and functional diversity of B lymphocytes, their regulatory roles independent of antibody production, and the molecular events that make this lineage unique are also considered. Finally, perturbations in B-cell development that give rise to certain types of congenital immunodeficiency, leukemia/lymphoma, and autoimmune disease are discussed in the context of normal B-cell development and selection. Despite the significant advances that have been made at the cellular and molecular levels, there is much more to learn, and cross-disciplinary studies in hematology and immunology will continue to pave the way for new discoveries.
Topics: Animals; Antigens, Differentiation, B-Lymphocyte; Autoimmune Diseases; B-Lymphocyte Subsets; B-Lymphocytes; Cell Differentiation; Cell Membrane; History, 20th Century; History, 21st Century; Humans; Immunologic Deficiency Syndromes; Leukemia; Lymphoma; Mice; Models, Immunological
PubMed: 18725575
DOI: 10.1182/blood-2008-02-078071 -
Current Allergy and Asthma Reports May 2014In this review we summarize recent insights into the development of human B cells primarily by studying immunodeficiencies. Development and differentiation of B cells... (Review)
Review
In this review we summarize recent insights into the development of human B cells primarily by studying immunodeficiencies. Development and differentiation of B cells can be considered as a paradigm for many other developmental processes in cell biology. However, it differs from the development of many other cell types by phases of extremely rapid cell division and by defined series of somatic recombination and mutation events required to assemble and refine the B cell antigen receptors. Both somatic DNA alteration and proliferation phases take place in defined sites but in different organs. Thus, cell migration and timely arrival at defined sites are additional features of B cell development. By comparing experimental mouse models with insights gained from studying defined genetic defects leading to primary immunodeficiencies and hypogammaglobulinemia, we address important features that are characteristic for human B cells. We also summarize recent advances made by developing improved in vitro and in vivo systems allowing the development of human B cells from hematopoietic stem cells. Combined with genetic and functional studies of immunodeficiencies, these models will contribute not only to a better understanding of disease affecting the B lymphocyte compartment, but also to designing better and safer novel B cell-targeted therapies in autoimmunity and allergy.
Topics: Animals; Antigens; B-Lymphocytes; Cell Differentiation; Cell Survival; Humans; Immunologic Memory; Transcription Factors
PubMed: 24633618
DOI: 10.1007/s11882-014-0434-8 -
Annual Review of Immunology 2012B cells are regarded for their capacity to produce antibody. However, recent advances in B cell biology have capitalized on old findings and demonstrated that B cells... (Review)
Review
B cells are regarded for their capacity to produce antibody. However, recent advances in B cell biology have capitalized on old findings and demonstrated that B cells also release a broad variety of cytokines. As with T helper cells, B cells can be classified into subsets according to the cytokine milieu that they produce. One functional B cell subset, regulatory B cells (Bregs), has recently been shown to contribute to the maintenance of the fine equilibrium required for tolerance. Bregs restrain the excessive inflammatory responses that occur during autoimmune diseases or that can be caused by unresolved infections. Pivotal to Breg function is interleukin-10 (IL-10), which inhibits proinflammatory cytokines and supports regulatory T cell differentiation. This review reports and discusses the factors that are important for Breg differentiation and for their effector function in both mouse and human.
Topics: Animals; Autoimmune Diseases; B-Lymphocyte Subsets; B-Lymphocytes; B-Lymphocytes, Regulatory; Cell Differentiation; Humans; T-Lymphocytes, Regulatory
PubMed: 22224776
DOI: 10.1146/annurev-immunol-020711-074934 -
International Reviews of Immunology Aug 2013Lupus is a complex autoimmune rheumatic disease of unknown aetiology. The disease is associated with diverse features of immunological abnormality in which B-lymphocytes... (Review)
Review
Lupus is a complex autoimmune rheumatic disease of unknown aetiology. The disease is associated with diverse features of immunological abnormality in which B-lymphocytes play a central role. However, the cause of atypical B-lymphocyte responses remains unclear. In this article, we provide a synopsis of current knowledge on intracellular signalling abnormalities in B-lymphocytes in lupus and their potential effects on the response of these cells in mouse models and in patients. There are numerous reported defects in the regulation of intracellular signalling proteins and pathways in B-lymphocytes in lupus that, potentially, affect critical biological responses. Most of the evidence for these defects comes from studies of disease models and genetically engineered mice. However, there is also increasing evidence from studying B-lymphocytes from patients and from genome-wide linkage analyses for parallel defects to those observed in mice. These studies provide molecular and genetic explanations for the key immunological abnormalities associated with lupus. Most of the new information appears to relate to defects in intracellular signalling that impact B-lymphocyte tolerance, cytokine production and responses to infections. Some of these abnormalities will be discussed within the context of disease pathogenesis.
Topics: Animals; B-Lymphocytes; Calcium Signaling; Humans; Immunity, Innate; Lupus Erythematosus, Systemic; Receptors, Immunologic; Signal Transduction
PubMed: 23768155
DOI: 10.3109/08830185.2013.788648 -
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 -
Immunologic Research Dec 2013B-lymphocytes are integral to host defense against microbial pathogens and are associated with many autoimmune diseases. The B-cell receptor implements B-cell... (Review)
Review
B-lymphocytes are integral to host defense against microbial pathogens and are associated with many autoimmune diseases. The B-cell receptor implements B-cell self-tolerance based on the antigen specificity, and B-cell-activating factor receptor (BAFF-R) imposes homeostatic control. While shaping the repertoire, the immune tolerance process also culls mature B cells into distinct populations. The activation response of B cells is tailored to the type of pathogen attack and is facilitated by T-cell help via CD40/CD40L interaction and/or innate cell help via toll-like receptors in conjunction with BAFF receptors and ligands. Activated effector B cells not only produce antibodies, but also produce a variety of cytokines to enhance and suppress the immune response. Not surprisingly, B cells play multiple roles in both humoral and cellular immune responses during infection and autoimmune pathogenesis. Here, we discuss how gene expression and signaling networks regulate peripheral B-cell tolerance, B-cell effector functions and emerging therapies targeting B-cell signaling in autoimmune diseases.
Topics: Agammaglobulinaemia Tyrosine Kinase; Animals; Apoptosis; Autoimmune Diseases; Autoimmunity; B-Lymphocyte Subsets; B-Lymphocytes; Homeostasis; Humans; Immune Tolerance; Immunity; Protein-Tyrosine Kinases; Receptors, Antigen, B-Cell; Signal Transduction
PubMed: 24293007
DOI: 10.1007/s12026-013-8466-z -
The New England Journal of Medicine Jul 1973
Topics: B-Lymphocytes; Clone Cells; Humans; Immunoglobulin M; Leukemia, Lymphoid; Neoplasms; T-Lymphocytes
PubMed: 4541228
DOI: 10.1056/NEJM197307192890310 -
Annals of the New York Academy of... Apr 1997
Review
Topics: Adult; Aging; Animals; B-Lymphocyte Subsets; B-Lymphocytes; Cell Differentiation; Cell Lineage; Humans; Immune Tolerance
PubMed: 9186636
DOI: 10.1111/j.1749-6632.1997.tb52041.x