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Frontiers in Immunology 2023Memory B cells and antibody-secreting cells are the two prime effector B cell populations that drive infection- and vaccine-induced long-term antibody-mediated immunity.... (Review)
Review
Memory B cells and antibody-secreting cells are the two prime effector B cell populations that drive infection- and vaccine-induced long-term antibody-mediated immunity. The antibody-mediated immunity mostly relies on the formation of specialized structures within secondary lymphoid organs, called germinal centers (GCs), that facilitate the interactions between B cells, T cells, and antigen-presenting cells. Antigen-activated B cells may proliferate and differentiate into GC-independent plasmablasts and memory B cells or differentiate into GC B cells. The GC B cells undergo proliferation coupled to somatic hypermutation of their immunoglobulin genes for antibody affinity maturation. Subsequently, affinity mature GC B cells differentiate into GC-dependent plasma cells and memory B cells. Here, we review how the NFκB signaling system controls B cell proliferation and the generation of GC B cells, plasmablasts/plasma cells, and memory B cells. We also identify and discuss some important unanswered questions in this connection.
Topics: Plasma Cells; B-Lymphocyte Subsets; Memory B Cells; B-Lymphocytes; Germinal Center
PubMed: 38169968
DOI: 10.3389/fimmu.2023.1185597 -
FEBS Letters Jun 2013Despite frequent exposures to a variety of potential triggers, including antigens produced by pathogens or commensal microbiota, B-lymphocytes are able to mount highly... (Review)
Review
Despite frequent exposures to a variety of potential triggers, including antigens produced by pathogens or commensal microbiota, B-lymphocytes are able to mount highly protective responses to a variety of threats, while remaining tolerant to self-components. A number of cytokines, signaling pathways and transcription factors have been characterized to elucidate the mechanisms underlying B cell tolerance to self. It is, however, unclear how the signals received by B-lymphocytes are converted into complex and sustained patterns of gene expression that can allow production of protective antibodies and maintain immune tolerance to self-components. Mounting evidence now suggests an important role for epigenetic mechanisms in modulating and transmitting signals for B lymphocyte tolerization to self-antigens. It is likely that a better insight into epigenetic regulation of B cell tolerance will lead to development of gene-specific therapeutic approaches that optimize host defense mechanisms to exogenous threats, while preventing development and/or progression of autoimmune inflammatory diseases.
Topics: Animals; Autoimmune Diseases; B-Lymphocytes; Chromatin; Epigenesis, Genetic; Humans; Immunoglobulins; Protein Processing, Post-Translational; Self Tolerance; V(D)J Recombination
PubMed: 23684644
DOI: 10.1016/j.febslet.2013.05.004 -
Current Opinion in Immunology Apr 2018The adult adaptive immune system is comprised of a wide spectrum of lymphocyte subsets with distinct antigen receptor repertoire profiles, effector functions, turnover... (Review)
Review
The adult adaptive immune system is comprised of a wide spectrum of lymphocyte subsets with distinct antigen receptor repertoire profiles, effector functions, turnover times and anatomical locations, acting in concert to provide optimal host protection and self-regulation. While some lymphocyte populations are replenished by bone marrow hematopoietic stem cells (HSCs) through adulthood, others emerge during a limited window of time during fetal and postnatal life and sustain through self-replenishment. Despite fundamental implications in immune regeneration, early life immunity and leukemogenesis, the impact of developmental timing on lymphocyte output remains an under explored frontier in immunology. In this review, we spotlight recent insights into the developmental changes in B cell output in mice and explore how several age specific cellular and molecular factors may shape the formation of a diverse adaptive immune system.
Topics: Age Factors; Animals; B-Lymphocyte Subsets; B-Lymphocytes; Biomarkers; Bone Marrow; Cell Differentiation; Cell Movement; Clonal Selection, Antigen-Mediated; Hematopoietic Stem Cells; Humans; Lymphopoiesis; Phenotype; RNA-Binding Proteins
PubMed: 29272734
DOI: 10.1016/j.coi.2017.12.005 -
Cellular & Molecular Immunology Mar 2013
Topics: Animals; Autoimmune Diseases; B-Lymphocytes; Bone Marrow Cells; Cell Differentiation; Cell Movement; Gene Rearrangement, B-Lymphocyte; Humans; Immunoglobulin Heavy Chains; Receptors, Antigen, B-Cell
PubMed: 23455016
DOI: 10.1038/cmi.2012.66 -
Molecular Medicine Reports Jul 2017Regulatory B cells (Bregs) are a subset of B cells, which reportedly exert significant immunomodulatory effects through the production of interleukin (IL)‑10, IL‑35... (Review)
Review
Regulatory B cells (Bregs) are a subset of B cells, which reportedly exert significant immunomodulatory effects through the production of interleukin (IL)‑10, IL‑35 and transforming growth factor‑β. Over the last decade, studies have indicated that Bregs function in autoimmune and allergic diseases through antigen‑specific and non‑specific immunoregulatory mechanisms. However, only a limited number of reviews have focused on the role of Bregs during infection, particularly their functions in intracellular infections. The present review discusses the role of Bregs in infectious diseases in animal models and human studies, and provides an overview of the immunoregulatory mechanisms used by Bregs.
Topics: Animals; Antigens, CD; B-Lymphocyte Subsets; B-Lymphocytes, Regulatory; Biomarkers; Communicable Diseases; Cytokines; Host-Parasite Interactions; Host-Pathogen Interactions; Humans; Immunomodulation; Phenotype
PubMed: 28534949
DOI: 10.3892/mmr.2017.6605 -
Current Opinion in Immunology Apr 2015The primary immunoglobulin repertoire develops via opposing forces of expanding diversification balanced by contracting selection mechanisms. The resulting shape is... (Review)
Review
The primary immunoglobulin repertoire develops via opposing forces of expanding diversification balanced by contracting selection mechanisms. The resulting shape is essential for host health and immune fitness. While the molecular mechanisms of Ig diversification have largely been defined, selection forces shaping emerging Ig repertoires are poorly understood. During lifetime, human and mouse early B cell development occurs at distinct locations-beginning in fetal liver before transferring to bone marrow and spleen by the end of gestation. During an early life window of time, the murine gut lamina propria harbors developing immature B cells in proximity to intestinal contents such as commensal microbes and dietary antigens. Location and timing of early B cell development may thus endow neighboring antigens with primary repertoire-shaping capabilities.
Topics: Animals; Antigens; B-Lymphocytes; Cell Differentiation; Clonal Selection, Antigen-Mediated; Gene Rearrangement, B-Lymphocyte; Humans; Immunity, Humoral; Immunoglobulins; Lymphocyte Activation; Peyer's Patches
PubMed: 25797714
DOI: 10.1016/j.coi.2015.02.011 -
IUBMB Life Oct 2011CD38 is a 45 kDa transmembrane receptor expressed in B lymphocytes and other cells from the immune system. It is involved in apoptosis, cell activation, differentiation,... (Review)
Review
CD38 is a 45 kDa transmembrane receptor expressed in B lymphocytes and other cells from the immune system. It is involved in apoptosis, cell activation, differentiation, and proliferation. CD38 has been used extensively to classify various subpopulations of lymphocytes in both humans and mice. It has also been used as a marker of poor prognosis in some lymphoid pathologies. However, CD38 is not a marker but rather an ectoenzyme and a receptor, where it performs several functions. The CD38 signaling pathway has only been partially studied in various cells of the immune system, where apparently the signaling is different depending on the lineage and differentiation state of the cell, leading to distinct outcomes. In this review, we provide an overview of well-established roles of CD38 signaling B lymphocytes from mice. We also discuss areas that need further clarification to get a broader image of how CD38 performs different functions in B cells and to understand its role in B lymphocyte biology under normal versus pathological conditions.
Topics: ADP-ribosyl Cyclase 1; Animals; B-Lymphocytes; Membrane Glycoproteins; Mice; Protein Conformation; Signal Transduction
PubMed: 21901817
DOI: 10.1002/iub.549 -
Experimental Gerontology May 2007The interplay of selective and homeostatic processes dominates the behavior of B lineage subsets following B cell antigen receptor (BCR) expression, and extends to... (Review)
Review
The interplay of selective and homeostatic processes dominates the behavior of B lineage subsets following B cell antigen receptor (BCR) expression, and extends to determinants of immune response quality and the persistence of immunologic memory. A key concept emerging from these considerations is that primary events acting upstream of mature B lymphocyte pools can profoundly impact downstream populations as the system attempts homeostatic adjustments. Since, advancing age is accompanied by profound changes in B cell generation and homeostasis, establishing the relative contributions of primary lesions versus compensatory homeostatic processes is critical to understanding these perturbations. Exploration of this problem requires an understanding of: (1) the identity, dynamics, and progenitor/successor relationships of marrow and peripheral B cell subsets; (2) the nature and interactions of selective and homeostatic processes acting in these subsets; (3) how these change with age. Our data show that BLyS and its receptors mediate peripheral B cell homeostasis, and that the size, dynamics and behavior of all B cell subsets influenced by B Lymphocyte Stimulator change with age. These findings suggest that homeostatic processes mediated through B Lymphocyte Stimulator are altered with age, and that these perturbations may primarily reflect compensatory homeostatic adjustments to upstream reductions in B cell generation.
Topics: Aging; B-Lymphocyte Subsets; B-Lymphocytes; Homeostasis; Humans; Precursor Cells, B-Lymphoid
PubMed: 17344004
DOI: 10.1016/j.exger.2007.01.010 -
Clinical and Experimental Immunology Jan 2015B-1 and B-2 B cell subsets carry out a diverse array of functions that range broadly from responding to innate stimuli, antigen presentation, cytokine secretion and... (Review)
Review
B-1 and B-2 B cell subsets carry out a diverse array of functions that range broadly from responding to innate stimuli, antigen presentation, cytokine secretion and antibody production. In this review, we first cover the functional roles of the major murine B cell subsets. We then highlight emerging evidence, primarily in preclinical rodent studies, to show that select B cell subsets are a therapeutic target in obesity and its associated co-morbidities. High fat diets promote accumulation of select murine B cell phenotypes in visceral adipose tissue. As a consequence, B cells exacerbate inflammation and thereby insulin sensitivity through the production of autoantibodies and via cross-talk with select adipose resident macrophages, CD4(+) and CD8(+) T cells. In contrast, interleukin (IL)-10-secreting regulatory B cells counteract the proinflammatory profile and improve glucose sensitivity. We subsequently review data from rodent studies that show pharmacological supplementation of obesogenic diets with long chain n-3 polyunsaturated fatty acids or specialized pro-resolving lipid mediators synthesized from endogenous n-3 polyunsaturated fatty acids boost B cell activation and antibody production. This may have potential benefits for improving inflammation in addition to combating the increased risk of viral infection that is an associated complication of obesity and type II diabetes. Finally, we propose potential underlying mechanisms throughout the review by which B cell activity could be differentially regulated in response to high fat diets.
Topics: Adipose Tissue; Animals; Antigens, Surface; B-Lymphocyte Subsets; B-Lymphocytes; Cell Differentiation; Comorbidity; Diet; Fatty Acids, Unsaturated; Humans; Immunity, Humoral; Inflammation; Obesity; Phenotype; T-Lymphocyte Subsets
PubMed: 25169121
DOI: 10.1111/cei.12444 -
Protein & Cell Jul 2011Mammalian target of rapamycin complex 2 (mTORC2) is a key downstream mediator of phosphoinositol-3-kinase (PI3K) dependent growth factor signaling. In lymphocytes,... (Review)
Review
Mammalian target of rapamycin complex 2 (mTORC2) is a key downstream mediator of phosphoinositol-3-kinase (PI3K) dependent growth factor signaling. In lymphocytes, mTORC2 has emerged as an important regulator of cell development, homeostasis and immune responses. However, our current understanding of mTORC2 functions and the molecular mechanisms regulating mTORC2 signaling in B and T cells are still largely incomplete. Recent studies have begun to shed light on this important pathway. We have previously reported that mTORC2 mediates growth factor dependent phosphorylation of Akt and facilitates Akt dependent phosphorylation and inactivation of transcription factors FoxO1 and FoxO3a. We have recently explored the functions of mTORC2 in B cells and show that mTORC2 plays a key role in regulating survival and immunoglobulin (Ig) gene recombination of bone marrow B cells through an Akt2-FoxO1 dependent mechanism. Ig recombination is suppressed in proliferating B cells to ensure that DNA double strand breaks are not generated in actively dividing cells. Our results raise the possibility that genetic or pharmacologic inhibition of mTORC2 may promote B cell tumor development as a result of inefficient suppression of Ig recombination in dividing B cells. We also propose a novel strategy to treat cancers based on our recent discovery that mTORC2 regulates Akt protein stability.
Topics: B-Lymphocytes; Cell Differentiation; Cell Transformation, Neoplastic; Humans; Transcription Factors
PubMed: 21822797
DOI: 10.1007/s13238-011-1077-3