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Clinical Reviews in Allergy & Immunology Oct 2017B lymphocytes are critical for effective immunity; they produce antibodies and cytokines, present antigens to T lymphocytes and regulate immune responses. However,... (Review)
Review
B lymphocytes are critical for effective immunity; they produce antibodies and cytokines, present antigens to T lymphocytes and regulate immune responses. However, because of the inherent randomness in the process of generating their vast repertoire of antigen-specific receptors, B cells can also cause diseases through recognizing and reacting to self. Therefore, B lymphocyte selection and responses require tight regulation at multiple levels and at all stages of their development and activation to avoid diseases. Indeed, newly generated B lymphocytes undergo rigorous tolerance mechanisms in the bone marrow and, subsequently, in the periphery after their migration. Furthermore, activation of mature B cells is regulated through controlled expression of co-stimulatory receptors and intracellular signalling thresholds. All these regulatory events determine whether and how B lymphocytes respond to antigens, by undergoing apoptosis or proliferation. However, defects that alter regulated co-stimulatory receptor expression or intracellular signalling thresholds can lead to diseases. For example, autoimmune diseases can result from altered regulation of B cell responses leading to the emergence of high-affinity autoreactive B cells, autoantibody production and tissue damage. The exact cause(s) of defective B cell responses in autoimmune diseases remains unknown. However, there is evidence that defects or mutations in genes that encode individual intracellular signalling proteins lead to autoimmune diseases, thus confirming that defects in intracellular pathways mediate autoimmune diseases. This review provides a synopsis of current knowledge of signalling proteins and pathways that regulate B lymphocyte responses and how defects in these could promote autoimmune diseases. Most of the evidence comes from studies of mouse models of disease and from genetically engineered mice. Some, however, also come from studying B lymphocytes from patients and from genome-wide association studies. Defining proteins and signalling pathways that underpin atypical B cell response in diseases will help in understanding disease mechanisms and provide new therapeutic avenues for precision therapy.
Topics: Animals; Autoimmunity; B-Lymphocytes; Humans; Immunity, Humoral; Immunomodulation; Intracellular Signaling Peptides and Proteins; Signal Transduction
PubMed: 28456914
DOI: 10.1007/s12016-017-8609-4 -
Clinical and Experimental Immunology Dec 2022Most B cells in the human body are present in tissues where they support immune responses to pathogens, vaccines, autoantigens, and tumours. Despite their clear... (Review)
Review
Most B cells in the human body are present in tissues where they support immune responses to pathogens, vaccines, autoantigens, and tumours. Despite their clear importance, they are very difficult to study and there are many areas of uncertainty that are difficult to resolve because of limited tissue access. In this review, we consider the zonal structure of lymphoid tissues, the B cell subsets they contain, and how these are regulated. We also discuss the impact that methods of deep interrogation have made on our current knowledge base, especially with respect to studies of cells from dissociated tissues. We discuss in some detail the controversial B cells with marginal zone distribution that some consider being archived memory B cells. We anticipate that more we understand of B cells in tissues and the niches they create, the more opportunities will be identified to harness their potential for therapeutic benefit.
Topics: Humans; B-Lymphocytes; Lymphoid Tissue; B-Lymphocyte Subsets; Autoantigens
PubMed: 36370126
DOI: 10.1093/cei/uxac101 -
Frontiers in Immunology 2021Aging is considered to be an important risk factor for several inflammatory diseases. B cells play a major role in chronic inflammatory diseases by antibody secretion,... (Review)
Review
Aging is considered to be an important risk factor for several inflammatory diseases. B cells play a major role in chronic inflammatory diseases by antibody secretion, antigen presentation and T cell regulation. Different B cell subsets have been implicated in infections and multiple autoimmune diseases. Since aging decreases B cell numbers, affects B cell subsets and impairs antibody responses, the aged B cell is expected to have major impacts on the development and progression of these diseases. In this review, we summarize the role of B cells in health and disease settings, such as atherosclerotic disease. Furthermore, we provide an overview of age-related changes in B cell development and function with respect to their impact in chronic inflammatory diseases.
Topics: Aging; Animals; Antibody Formation; Autoimmune Diseases; B-Lymphocyte Subsets; B-Lymphocytes; Cellular Senescence; Humans; Inflammation; Lymphocyte Activation
PubMed: 34675924
DOI: 10.3389/fimmu.2021.733566 -
Frontiers in Immunology 2022Acute on chronic liver failure (ACLF) is characterized by the immunologic dissonance during the prolonged pathogenic development. Both abnormal innate immune response...
BACKGROUND AND OBJECTIVES
Acute on chronic liver failure (ACLF) is characterized by the immunologic dissonance during the prolonged pathogenic development. Both abnormal innate immune response and adaptive T-cell response have been reported in patients with ACLF; however, less is known regarding B cells in ACLF pathogenesis. Previous reports were only based on immunophenotyping of peripheral blood samples. Here, we aim to dissect liver-infiltrating B-cell subpopulation in ACLF.
METHODS
Paired liver perfusate and peripheral blood were freshly collected from healthy living donors and recipients during liver transplantation. Liver tissues were obtained from patients with ACLF, cirrhosis, and healthy controls. Flow cytometry was used to characterize the phenotypic and functional alterations in intrahepatic and circulating B-cell populations from ACLF, cirrhosis, and healthy controls. The expression of CD19 and CD138 on liver tissues was examined by immunohistochemistry staining.
RESULTS
In this study, we first deciphered the intrahepatic B cells subsets of patients with ACLF. We found that the ACLF liver harbored reduced fraction of naïve B cells and elevated percentage of CD27CD21 activated memory B cells (AM), CD27CD21 atypical memory B cells (atMBC), CD27IgDIgM(IgM memory B cells), and CD27CD38 plasma cells than cirrhosis and healthy controls. Moreover, these B subpopulations demonstrated enhanced activation and altered effector functions. Specifically, the ACLF liver was abundant in atMBC expressing higher CD11c and lower CD80 molecule, which was significantly correlated to alanine aminotransferase and aspartate aminotransferase. In addition, we found that intrahepatic CD27CD38plasma cells were preferentially accumulated in ACLF, which expressed more CD273 (PD-L2) and secreted higher granzyme B and IL-10. Finally, the enriched hepatic plasma B cells were in positive association with disease severity indices including alkaline phosphatase and gamma-glutamyl transferase.
CONCLUSIONS
In this pilot study, we showed an intrahepatic B-cell landscape shaped by the ACLF liver environment, which was distinct from paired circulating B-cell subsets. The phenotypic and functional perturbation in atMBC and plasma cells highlighted the unique properties of infiltrating B cells during ACLF progression, thereby denoting the potential of B-cell intervention in ACLF therapy.
Topics: Humans; Acute-On-Chronic Liver Failure; Pilot Projects; B-Lymphocytes; Plasma Cells; B-Lymphocyte Subsets; Liver Cirrhosis
PubMed: 36505417
DOI: 10.3389/fimmu.2022.1041176 -
Journal of Dermatological Science Jan 2019B cells have moved to the center stage in many autoimmune diseases including autoantibody-mediated diseases and T cell-mediated autoimmune diseases such as rheumatoid... (Review)
Review
B cells have moved to the center stage in many autoimmune diseases including autoantibody-mediated diseases and T cell-mediated autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. B cells play an important role for immune response beyond antibody production through mechanisms like antigen presentation and cytokine production. However, not all B cells positively regulate immune responses. Regulatory B cells negatively regulate immune responses by production of anti-inflammatory cytokines such as IL-10, IL-35, and TGF-β. Regulatory B cells have been found to be decreased and/or functionally impaired in various autoimmune diseases. In contrast, B cells also produce pro-inflammatory cytokines, such as IL-6, IFN-γ and GM - CSF. These effector B cells contribute to the pathogenesis of autoimmune diseases. Regulatory and effector B cell balance regulates immune response through the release of cytokines. Furthermore, a protocol that selectively depletes effector B cells while sparing regulatory B cells would represent a potent therapy for autoimmune diseases rather than pan-B cell depletion using anti-CD20 mAb.
Topics: B-Lymphocyte Subsets; B-Lymphocytes, Regulatory; Cytokines; Humans; Immunity, Cellular; Immunotherapy; Inflammation Mediators; Lupus Erythematosus, Systemic; Scleroderma, Systemic
PubMed: 30514664
DOI: 10.1016/j.jdermsci.2018.11.008 -
Mucosal Immunology Jan 2021Food allergies are a major public health concern due to their widespread and rising prevalence. The increase in food allergy is partially due to Western lifestyle habits... (Review)
Review
Food allergies are a major public health concern due to their widespread and rising prevalence. The increase in food allergy is partially due to Western lifestyle habits which deplete protective commensal microbiota. These microbial perturbations can result in adverse host-microbe interactions, altering the phenotype of various immune cells and instigating allergic sensitization. Although B cells are critical to allergic pathology, microbial influences on B cells have been somewhat overlooked. Here, we focus on direct and indirect interactions between bacteria and B cells and how such interactions regulate B-cell phenotype, namely antibody production (IgA, IgE, IgG1, and IgG4) and regulatory B-cell (Breg) function. Understanding how microbes modulate B-cell activity in the context of food allergies is critical to both tracing the development of disease and assessing future treatment options.
Topics: Animals; Antibody Formation; B-Lymphocyte Subsets; B-Lymphocytes; Disease Susceptibility; Food Hypersensitivity; Host Microbial Interactions; Humans; Microbiota
PubMed: 33106585
DOI: 10.1038/s41385-020-00350-x -
European Cytokine Network Mar 2013B cells regulate immune responses during infectious, inflammatory and autoimmune diseases. Beside their unique and characteristic antibody production, B lymphocytes can... (Review)
Review
B cells regulate immune responses during infectious, inflammatory and autoimmune diseases. Beside their unique and characteristic antibody production, B lymphocytes can modulate physiological and pathological processes by presenting antigens or synthesizing signaling molecules. In human and mouse diseases, immuno-intervention, targeting B cells, has revealed and highlighted their antibody-independent regulatory contribution. In this review, we focus on B cell-cytokine production, which is commonly disturbed in inflammatory disorders, and describe the B cell cytokine profile in different diseases. Finally, we discuss some key issues for future B cell-targeted therapies.
Topics: Animals; B-Lymphocytes; Cytokines; Disease; Humans
PubMed: 23614878
DOI: 10.1684/ecn.2013.0327 -
Journal of Immunology (Baltimore, Md. :... Nov 2017A small population of B cells exists in lymphoid tissues and body cavities of mice that is distinct in development, phenotype, and function from the majority (B-2) B... (Review)
Review
A small population of B cells exists in lymphoid tissues and body cavities of mice that is distinct in development, phenotype, and function from the majority (B-2) B cell population. This population, originally termed "Ly-1" and now "B-1," has received renewed interest as an innate-like B cell population of fetal-derived hematopoiesis, responsible for natural Ab production and rapid immune responses. Molecular analyses have begun to define fetal and adult hematopoiesis, while cell-fate mapping studies have revealed complex developmental origins of B-1 cells. Together the studies provide a more detailed understanding of B-1 cell regulation and function. This review outlines studies that defined B-1 cells as natural Ab- and cytokine-producing B cells of fetal origin, with a focus on work conducted by R.R. Hardy, an early pioneer and codiscoverer of B-1 cells, whose seminal contributions enhanced our understanding of this enigmatic B cell population.
Topics: Animals; Antibody Formation; B-Lymphocyte Subsets; B-Lymphocytes; CD5 Antigens; Cell Differentiation; Fetal Development; Hematopoiesis; Humans; Immunity, Humoral; Immunity, Innate; Mice
PubMed: 29109178
DOI: 10.4049/jimmunol.1700943 -
Frontiers in Immunology 2023To date, studies of tissue-resident immunity have mainly focused on innate immune cells and T cells, with limited data on B cells. B-1 B cells are a unique subset of B... (Review)
Review
To date, studies of tissue-resident immunity have mainly focused on innate immune cells and T cells, with limited data on B cells. B-1 B cells are a unique subset of B cells with innate-like properties, enriched in murine pleural and peritoneal cavities and distinct from conventional B-2 cells in their ontogeny, phenotype and function. Here we discuss how B-1 cells represent exemplar tissue-resident immune cells, summarizing the evidence for their long-term persistence & self-renewal within tissues, differential transcriptional programming shaped by organ-specific environmental cues, as well as their tissue-homeostatic functions. Finally, we review the emerging data supporting the presence and homeostatic role of B-1 cells across non-lymphoid organs (NLOs) both in mouse and human.
Topics: Humans; Animals; Mice; B-Lymphocyte Subsets; B-Lymphocytes; Cues; Homeostasis; Peritoneal Cavity
PubMed: 37744333
DOI: 10.3389/fimmu.2023.1106294 -
Journal of Molecular Biology Jan 2021It is now appreciated that in addition to their role in humoral immunity, B cells also exert regulatory mechanisms that lead to attenuation of inflammatory responses.... (Review)
Review
It is now appreciated that in addition to their role in humoral immunity, B cells also exert regulatory mechanisms that lead to attenuation of inflammatory responses. The concept of B-cell regulation became well recognized when mice deficient in B cells due to genetic disruption were shown to be refractory to recovery from the signs of experimental autoimmune encephalomyelitis (EAE), the mouse model of multiple sclerosis. This seminal study spurred the search for B-cell regulatory phenotypes and mechanisms of action. Our approach was to utilize differential B-cell depletion with anti-CD20 to retain B cells whose presence were required to achieve EAE recovery. Utilizing flow cytometry, adoptive cell therapy and genetic approaches, we discovered a new B-cell subset that, upon adoptive transfer into B cell-deficient mice, was sufficient to promote EAE recovery. This B-cell subset is IgM, but due to low/negative IgD cell surface expression, it was named B-cell IgD low (BD). Mechanistically, we found that in the absence of BD, the absolute cell number of CD4Foxp3 T regulatory cells (Treg), essential for immune tolerance, was significantly reduced. Furthermore, we found that BD expression of glucocorticoid-induced tumor necrosis factor ligand (GITRL) was essential for induction of Treg proliferation and maintenance of their homeostasis. Thus, we have identified a new B-cell subset that is critical for immunological tolerance through interactions with Treg.
Topics: Animals; Antibody Formation; Autoimmunity; B-Lymphocyte Subsets; B-Lymphocytes; Glucocorticoids; Homeostasis; Humans; Immune Tolerance; Immunoglobulin D; Immunomodulation; Lymphocyte Depletion; T-Lymphocytes, Regulatory
PubMed: 32615130
DOI: 10.1016/j.jmb.2020.06.023