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European Journal of Immunology Jul 2018IgD emerged soon after IgM at the time of inception of the adaptive immune system. Despite its evolutionary conservation from fish to humans, the specific functions of... (Review)
Review
IgD emerged soon after IgM at the time of inception of the adaptive immune system. Despite its evolutionary conservation from fish to humans, the specific functions of IgD have only recently begun to be elucidated. Mature B cells undergo alternative mRNA splicing to express IgD and IgM receptors with identical antigenic specificity. The enigma of dual IgD and IgM expression has been tackled by several recent studies showing that IgD helps peripheral accumulation of physiologically autoreactive B cells through its functional unresponsiveness to self-antigens but prompt readiness against foreign antigens. IgD achieves this balance by attenuating IgM-mediated anergy while promoting specific responses to multimeric non-self-antigens. Additional research has clarified how and why certain mucosal B cells become plasmablasts or plasma cells specializing in IgD secretion. In particular, the microbiota has been shown to play an important role in driving class switch-mediated replacement of IgM with IgD. Secreted IgD appears to enhance mucosal homeostasis and immune surveillance by "arming" myeloid effector cells such as basophils and mast cells with IgD antibodies reactive against mucosal antigens, including commensal and pathogenic microbes. Here we will review these advances and discuss their implications in humoral immunity in human and mice.
Topics: Animals; Antigens; Antigens, Bacterial; Autoimmunity; Homeostasis; Humans; Immunoglobulin D; Immunoglobulin M; Mice; Microbiota; Mucous Membrane; Myeloid Cells
PubMed: 29733429
DOI: 10.1002/eji.201646547 -
Frontiers in Immunology 2022Antibodies play a critical role in linking the adaptive immune response to the innate immune system. In humans, antibodies are categorized into five classes, IgG, IgM,... (Review)
Review
Antibodies play a critical role in linking the adaptive immune response to the innate immune system. In humans, antibodies are categorized into five classes, IgG, IgM, IgA, IgE, and IgD, based on constant region sequence, structure, and tropism. In serum, IgG is the most abundant antibody, comprising 75% of antibodies in circulation, followed by IgA at 15%, IgM at 10%, and IgD and IgE are the least abundant. All human antibody classes are post-translationally modified by sugars. The resulting glycans take on many divergent structures and can be attached in an N-linked or O-linked manner, and are distinct by antibody class, and by position on each antibody. Many of these glycan structures on antibodies are capped by sialic acid. It is well established that the composition of the N-linked glycans on IgG exert a profound influence on its effector functions. However, recent studies have described the influence of glycans, particularly sialic acid for other antibody classes. Here, we discuss the role of glycosylation, with a focus on terminal sialylation, in the biology and function across all antibody classes. Sialylation has been shown to influence not only IgG, but IgE, IgM, and IgA biology, making it an important and unappreciated regulator of antibody function.
Topics: Humans; Immunoglobulin A; Immunoglobulin D; Immunoglobulin E; Immunoglobulin G; Immunoglobulin M; N-Acetylneuraminic Acid; Polysaccharides
PubMed: 35464485
DOI: 10.3389/fimmu.2022.818736 -
Nature Reviews. Immunology Jul 2020Humoral immune responses at mucosal surfaces have historically focused on IgA. Growing evidence highlights the complexity of IgA-inducing pathways and the functional... (Review)
Review
Humoral immune responses at mucosal surfaces have historically focused on IgA. Growing evidence highlights the complexity of IgA-inducing pathways and the functional impact of IgA on mucosal commensal bacteria. In the gut, IgA contributes to the establishment of a mutualistic host-microbiota relationship that is required to maintain homeostasis and prevent disease. This Review discusses how mucosal IgA responses occur in an increasingly complex humoral defence network that also encompasses IgM, IgG and IgD. Aside from integrating the protective functions of IgA, these hitherto neglected mucosal antibodies may strengthen the communication between mucosal and systemic immune compartments.
Topics: Animals; Antibodies, Bacterial; Bacteria; Humans; Immunity, Mucosal; Immunoglobulin A; Immunoglobulin D; Immunoglobulin G; Immunoglobulin M; Intestinal Mucosa
PubMed: 32015473
DOI: 10.1038/s41577-019-0261-1 -
Frontiers in Immunology 2019The increasingly recognized role of different types of B cells and plasma cells in protective and pathogenic immune responses combined with technological advances have... (Review)
Review
The increasingly recognized role of different types of B cells and plasma cells in protective and pathogenic immune responses combined with technological advances have generated a plethora of information regarding the heterogeneity of this human immune compartment. Unfortunately, the lack of a consistent classification of human B cells also creates significant imprecision on the adjudication of different phenotypes to well-defined populations. Additional confusion in the field stems from: the use of non-discriminatory, overlapping markers to define some populations, the extrapolation of mouse concepts to humans, and the assignation of functional significance to populations often defined by insufficient surface markers. In this review, we shall discuss the current understanding of human B cell heterogeneity and define major parental populations and associated subsets while discussing their functional significance. We shall also identify current challenges and opportunities. It stands to reason that a unified approach will not only permit comparison of separate studies but also improve our ability to define deviations from normative values and to create a clean framework for the identification, functional significance, and disease association with new populations.
Topics: Animals; B-Lymphocytes; B-Lymphocytes, Regulatory; Cytokines; Humans; Immunity, Humoral; Immunoglobulin D; Immunoglobulin M; Immunologic Memory; Plasma Cells
PubMed: 31681331
DOI: 10.3389/fimmu.2019.02458 -
Current Opinion in Immunology Jun 2011Recent discoveries of IgD in ancient vertebrates suggest that IgD has been preserved in evolution from fish to human for important immunological functions. A... (Review)
Review
Recent discoveries of IgD in ancient vertebrates suggest that IgD has been preserved in evolution from fish to human for important immunological functions. A non-canonical form of class switching from IgM to IgD occurs in the human upper respiratory mucosa to generate IgD-secreting B cells that bind respiratory bacteria and their products. In addition to enhancing mucosal immunity, IgD class-switched B cells enter the circulation to 'arm' basophils and other innate immune cells with secreted IgD. Although the nature of the IgD receptor remains elusive, cross-linking of IgD on basophils stimulates release of immunoactivating, proinflammatory and antimicrobial mediators. This pathway is dysregulated in autoinflammatory disorders such as hyper-IgD syndrome, indicating that IgD orchestrates an ancestral surveillance system at the interface between immunity and inflammation.
Topics: Alternative Splicing; Animals; Evolution, Molecular; Humans; Immunoglobulin Class Switching; Immunoglobulin D; Signal Transduction
PubMed: 21353515
DOI: 10.1016/j.coi.2011.01.006 -
Immunity Mar 2021
Topics: Allergy and Immunology; Gene Expression Regulation; History, 20th Century; History, 21st Century; Humans; Immunoglobulin D; Male; NF-kappa B; Signal Transduction; United States
PubMed: 33691124
DOI: 10.1016/j.immuni.2021.02.009 -
Journal of Medical Genetics Mar 1974
Review
Topics: Age Factors; Animals; Chemical Phenomena; Chemistry; Climate; Epitopes; Female; Genetic Code; Humans; Immunoglobulin A; Immunoglobulin D; Immunoglobulin E; Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Male; Pregnancy; Protein Conformation; Sex Factors
PubMed: 4134621
DOI: 10.1136/jmg.11.1.80 -
Clinical and Experimental Immunology Mar 2021The clinical application of monoclonal antibodies (mAbs) has revolutionized the field of cancer therapy, as it has enabled the successful treatment of previously... (Review)
Review
The clinical application of monoclonal antibodies (mAbs) has revolutionized the field of cancer therapy, as it has enabled the successful treatment of previously untreatable types of cancer. Different mechanisms play a role in the anti-tumour effect of mAbs. These include blocking of tumour-specific growth factor receptors or of immune modulatory molecules as well as complement and cell-mediated tumour cell lysis. Thus, for many mAbs, Fc-mediated effector functions critically contribute to the efficacy of treatment. As immunoglobulin (Ig) isotypes differ in their ability to bind to Fc receptors on immune cells as well as in their ability to activate complement, they differ in the immune responses they activate. Therefore, the choice of antibody isotype for therapeutic mAbs is dictated by its intended mechanism of action. Considering that clinical efficacy of many mAbs is currently achieved only in subsets of patients, optimal isotype selection and Fc optimization during antibody development may represent an important step towards improved patient outcome. Here, we discuss the current knowledge of the therapeutic effector functions of different isotypes and Fc-engineering strategies to improve mAbs application.
Topics: Antibodies, Monoclonal; Cytotoxicity, Immunologic; Humans; Immunoglobulin A; Immunoglobulin D; Immunoglobulin E; Immunoglobulin G; Immunoglobulin Isotypes; Immunoglobulin M; Neoplasms
PubMed: 33155272
DOI: 10.1111/cei.13545 -
Immunological Reviews Sep 2010Immunoglobulin D (IgD) has remained a mysterious antibody class for almost half a century. IgD was initially thought to be a recently evolved Ig isotype expressed only... (Review)
Review
Immunoglobulin D (IgD) has remained a mysterious antibody class for almost half a century. IgD was initially thought to be a recently evolved Ig isotype expressed only by some mammalian species, but recent discoveries in fishes and amphibians demonstrate that IgD was present in the ancestor of all jawed vertebrates and has important immunological functions. The structure of IgD has been very dynamic throughout evolution. Mammals can express IgD through alternative splicing and class switch recombination. Active cell-dependent and T-cell-independent IgM-to-IgD class switching takes place in a unique subset of human B cells from the upper aerodigestive mucosa, which provides a layer of mucosal protection by interacting with many pathogens and their virulence factors. Circulating IgD can bind to myeloid cells such as basophils and induce antimicrobial, inflammatory, and B-cell-stimulating factors upon cross-linking, which contributes to not only immune surveillance but also inflammation and tissue damage when this pathway is overactivated under pathological conditions. Recent research shows that IgD is an important immunomodulator that orchestrates an ancestral surveillance system at the interface between immunity and inflammation.
Topics: Amino Acid Sequence; Animals; B-Lymphocytes; Humans; Immunoglobulin D; Immunoglobulin G; Immunoglobulin Isotypes; Molecular Sequence Data; Sequence Alignment
PubMed: 20727035
DOI: 10.1111/j.1600-065X.2010.00929.x -
Oncology (Williston Park, N.Y.) Aug 2013Immunoglobulin D multiple myeloma (IgD MM) accounts for almost 2% of all myeloma cases. It is associated with an increased frequency of undetectable or small monoclonal... (Review)
Review
Immunoglobulin D multiple myeloma (IgD MM) accounts for almost 2% of all myeloma cases. It is associated with an increased frequency of undetectable or small monoclonal (M)-protein levels on electrophoresis; osteolytic lesions; extramedullary involvement; amyloidosis; a lambda (lambda) light chain predilection; renal failure; hypercalcemia; and, often, advanced disease at diagnosis. Immunoglobulin E (IgE) MM is rare, with fewer than 50 cases reported in the literature. IgE MM presents with features similar to those of IgD MM, along with a higher incidence of plasma cell leukemia. The hallmark of IgE MM is t(11;14) (q13;q32). IgD and IgE levels are generally very low and hence may escape detection; thus, it is important that, when myeloma is suspected, patients be screened for the presence of IgD and IgE if they have an apparently free monoclonal immunoglobulin light chain in the serum. Although survival of patients with IgD MM or IgE MM is shorter in comparison to those with immunoglobulin G (IgG) MM or immunoglobulin A (IgA) MM, the outcome for patients with IgD and IgE subtypes is improving with the use of novel agents and autologous transplantation.
Topics: Humans; Immunoglobulin D; Immunoglobulin E; Immunoglobulin Light Chains; Immunoglobulin lambda-Chains; Multiple Myeloma
PubMed: 24133829
DOI: No ID Found