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Frontiers in Immunology 2022Multiple sclerosis (MS), a debilitating autoimmune inflammatory disease that affects the brain and spinal cord, causes demyelination of neurons, axonal damage, and... (Review)
Review
Multiple sclerosis (MS), a debilitating autoimmune inflammatory disease that affects the brain and spinal cord, causes demyelination of neurons, axonal damage, and neurodegeneration. MS and the murine experimental autoimmune encephalomyelitis (EAE) model have been viewed mainly as T-cell-mediated diseases. Emerging data have suggested the contribution of B-cells and autoantibodies to the disease progression. However, the underlying mechanisms by which dysregulated B-cells and antibody response promote MS and EAE remain largely unclear. Here, we provide an updated review of this specific subject by including B-cell biology and the role of B-cells in triggering autoimmune neuroinflammation with a focus on the regulation of antibody-producing B-cells. We will then discuss the role of a specific type of antibody, IgE, as it relates to the potential regulation of microglia and macrophage activation, autoimmunity and MS/EAE development. This knowledge can be utilized to develop new and effective therapeutic approaches to MS, which fits the scope of the Research Topic "Immune Mechanism in White Matter Lesions: Clinical and Pathophysiological Implications".
Topics: Animals; Antibody Formation; B-Lymphocytes; Encephalomyelitis, Autoimmune, Experimental; Immunoglobulin E; Mice; Multiple Sclerosis
PubMed: 35784370
DOI: 10.3389/fimmu.2022.900117 -
Frontiers in Immunology 2022Epithelial barriers, which include the gastrointestinal, respiratory, and genitourinary mucosa, compose the body's front line of defense. Since barrier tissues are... (Review)
Review
Epithelial barriers, which include the gastrointestinal, respiratory, and genitourinary mucosa, compose the body's front line of defense. Since barrier tissues are persistently exposed to microbial challenges, a rapid response that can deal with diverse invading pathogens is crucial. Because B cells have been perceived as indirectly contributing to immune responses through antibody production, B cells functioning in the peripheral organs have been outside the scope of researchers. However, recent evidence supports the existence of tissue-resident memory B cells (BRMs) in the lungs. This population's defensive response was stronger and faster than that of their circulating counterparts and could resist heterogeneous strains. With such traits, BRMs could be a promising target for vaccine design, but much about them remains to be revealed, including their locations, origin, specific markers, and the mechanisms of their establishment and maintenance. There is evidence for resident B cells in organs other than the lungs, suggesting that B cells are directly involved in the immune reactions of multiple non-lymphoid organs. This review summarizes the history of the discovery of BRMs and discusses important unresolved questions. Unique characteristics of humoral immunity that play an important role in the peripheral organs will be described briefly. Future research on B cells residing in non-lymphoid organs will provide new insights to help solve major problems regarding human health.
Topics: Antibody Formation; B-Lymphocytes; Humans; Immunity, Humoral; Memory B Cells; Mucous Membrane
PubMed: 35924234
DOI: 10.3389/fimmu.2022.953088 -
Immunity Jan 2022The immune response is an amalgam of heritable and non-heritable effects, although the contribution of each is generally unknown. In this issue of Immunity, Venkataraman...
The immune response is an amalgam of heritable and non-heritable effects, although the contribution of each is generally unknown. In this issue of Immunity, Venkataraman et al. report heritable traits that govern anti-viral antibody epitope specificity and breadth controlled by the MHC class II region, indicating that your genes influence which pathogen-derived epitopes your B cells target during viral infections.
Topics: Antibodies, Viral; Antibody Formation; Antiviral Agents; B-Lymphocytes; Epitopes
PubMed: 35021059
DOI: 10.1016/j.immuni.2021.12.008 -
Infection Feb 2022The coronavirus disease 2019 (COVID-19), caused by the novel betacoronavirus severe acute respiratory syndrome 2 (SARS-CoV-2), was declared a pandemic in March 2020. Due... (Review)
Review
OBJECTIVES
The coronavirus disease 2019 (COVID-19), caused by the novel betacoronavirus severe acute respiratory syndrome 2 (SARS-CoV-2), was declared a pandemic in March 2020. Due to the continuing surge in incidence and mortality globally, determining whether protective, long-term immunity develops after initial infection or vaccination has become critical.
METHODS/RESULTS
In this narrative review, we evaluate the latest understanding of antibody-mediated immunity to SARS-CoV-2 and to other coronaviruses (SARS-CoV, Middle East respiratory syndrome coronavirus and the four endemic human coronaviruses) in order to predict the consequences of antibody waning on long-term immunity against SARS-CoV-2. We summarise their antibody dynamics, including the potential effects of cross-reactivity and antibody waning on vaccination and other public health strategies. At present, based on our comparison with other coronaviruses we estimate that natural antibody-mediated protection for SARS-CoV-2 is likely to last for 1-2 years and therefore, if vaccine-induced antibodies follow a similar course, booster doses may be required. However, other factors such as memory B- and T-cells and new viral strains will also affect the duration of both natural and vaccine-mediated immunity.
CONCLUSION
Overall, antibody titres required for protection are yet to be established and inaccuracies of serological methods may be affecting this. We expect that with standardisation of serological testing and studies with longer follow-up, the implications of antibody waning will become clearer.
Topics: Antibody Formation; COVID-19; Humans; Middle East Respiratory Syndrome Coronavirus; Pandemics; SARS-CoV-2
PubMed: 34324165
DOI: 10.1007/s15010-021-01664-z -
International Journal of Molecular... Aug 2020A functional adaptive immune response is the major determinant for clearance of hepatitis C virus (HCV) infection. However, in the majority of patients, this response... (Review)
Review
A functional adaptive immune response is the major determinant for clearance of hepatitis C virus (HCV) infection. However, in the majority of patients, this response fails and persistent infection evolves. Here, we dissect the HCV-specific key players of adaptive immunity, namely B cells and T cells, and describe factors that affect infection outcome. Once chronic infection is established, continuous exposure to HCV antigens affects functionality, phenotype, transcriptional program, metabolism, and the epigenetics of the adaptive immune cells. In addition, viral escape mutations contribute to the failure of adaptive antiviral immunity. Direct-acting antivirals (DAA) can mediate HCV clearance in almost all patients with chronic HCV infection, however, defects in adaptive immune cell populations remain, only limited functional memory is obtained and reinfection of cured individuals is possible. Thus, to avoid potential reinfection and achieve global elimination of HCV infections, a prophylactic vaccine is needed. Recent vaccine trials could induce HCV-specific immunity but failed to protect from persistent infection. Thus, lessons from natural protection from persistent infection, DAA-mediated cure, and non-protective vaccination trials might lead the way to successful vaccination strategies in the future.
Topics: Adaptive Immunity; Animals; Antibody Formation; Clinical Trials as Topic; Hepacivirus; Humans; T-Lymphocytes; Viral Vaccines
PubMed: 32781731
DOI: 10.3390/ijms21165644 -
Frontiers in Immunology 2020The continuous development of molecular biology and protein engineering technologies enables the expansion of the breadth and complexity of protein therapeutics for... (Review)
Review
The continuous development of molecular biology and protein engineering technologies enables the expansion of the breadth and complexity of protein therapeutics for administration. However, the immunogenicity and associated development of antibodies against therapeutics are a major restriction factor for their usage. The B cell follicular and particularly germinal center areas in secondary lymphoid organs are the anatomical sites where the development of antibody responses against pathogens and immunogens takes place. A growing body of data has revealed the importance of the orchestrated function of highly differentiated adaptive immunity cells, including follicular helper CD4 T cells and germinal center B cells, for the optimal generation of these antibody responses. Understanding the cellular and molecular mechanisms mediating the antibody responses against therapeutics could lead to novel strategies to reduce their immunogenicity and increase their efficacy.
Topics: Animals; Antibody Formation; Antigens; B-Lymphocytes; Drug Therapy; Germinal Center; Humans; Immunity, Humoral; Lymph Nodes; Mice
PubMed: 32477334
DOI: 10.3389/fimmu.2020.00791 -
Trends in Immunology Sep 2015Activation-induced cytidine deaminase (AID) mediates cytosine deamination and underlies two central processes in antibody diversification: somatic hypermutation and... (Review)
Review
Activation-induced cytidine deaminase (AID) mediates cytosine deamination and underlies two central processes in antibody diversification: somatic hypermutation and class-switch recombination. AID deamination is not exclusive to immunoglobulin loci; it can instigate DNA lesions in non-immunoglobulin genes and thus stringent checks are in place to constrain and restrict its activity. Recent findings have provided new insights into the mechanisms that target AID activity to specific genomic regions, revealing an involvement for noncoding RNAs associated with polymerase pausing and with enhancer transcription as well as genomic architecture. We review these findings and integrate them into a model for multilevel regulation of AID expression and targeting in immunoglobulin and non-immunoglobulin loci. Within this framework we discuss gaps in understanding, and outline important areas of further research.
Topics: Animals; Antibody Formation; Cytidine Deaminase; Gene Expression Regulation; Genetic Loci; Humans; Immunoglobulin Class Switching; Immunoglobulins; Protein Binding; Protein Interaction Domains and Motifs; Transcription Factors
PubMed: 26254147
DOI: 10.1016/j.it.2015.07.003 -
Cells Mar 2020As a non-antibody scaffold, monobodies based on the fibronectin type III (FN3) domain overcome antibody size and complexity while maintaining analogous binding loops.... (Review)
Review
As a non-antibody scaffold, monobodies based on the fibronectin type III (FN3) domain overcome antibody size and complexity while maintaining analogous binding loops. However, antibodies and their derivatives remain the gold standard for the design of new therapeutics. In response, clinical-stage therapeutic proteins based on the FN3 domain are beginning to use native fibronectin function as a point of differentiation. The small and simple structure of monomeric monobodies confers increased tissue distribution and reduced half-life, whilst the absence of disulphide bonds improves stability in cytosolic environments. Where multi-specificity is challenging with an antibody format that is prone to mis-pairing between chains, multiple FN3 domains in the fibronectin assembly already interact with a large number of molecules. As such, multiple monobodies engineered for interaction with therapeutic targets are being combined in a similar beads-on-a-string assembly which improves both efficacy and pharmacokinetics. Furthermore, full length fibronectin is able to fold into multiple conformations as part of its natural function and a greater understanding of how mechanical forces allow for the transition between states will lead to advanced applications that truly differentiate the FN3 domain as a therapeutic scaffold.
Topics: Amino Acid Sequence; Antibodies; Antibody Formation; Fibronectin Type III Domain; Fibronectins; Humans; Protein Binding
PubMed: 32143310
DOI: 10.3390/cells9030610 -
Molecular Immunology Oct 2014Antibodies, forming immune complexes with their specific antigen, can cause complete suppression or several 100-fold enhancement of the antibody response. Immune... (Review)
Review
Antibodies, forming immune complexes with their specific antigen, can cause complete suppression or several 100-fold enhancement of the antibody response. Immune complexes containing IgG and IgM may activate complement and in such situations also complement components will be part of the immune complex. Here, we review experimental data on how antibodies via the complement system upregulate specific antibody responses. Current data suggest that murine IgG1, IgG2a, and IgG2b upregulate antibody responses primarily via Fc-receptors and not via complement. In contrast, IgM and IgG3 act via complement and require the presence of complement receptors 1 and 2 (CR1/2) expressed on both B cells and follicular dendritic cells. Complement plays a crucial role for antibody responses not only to antigen complexed to antibodies, but also to antigen administered alone. Lack of C1q, but not of Factor B or MBL, severely impairs antibody responses suggesting involvement of the classical pathway. In spite of this, normal antibody responses are found in mice lacking several activators of the classical pathway (complement activating natural IgM, serum amyloid P component (SAP), specific intracellular adhesion molecule-grabbing non-integrin R1 (SIGN-R1) or C-reactive protein. Possible explanations to these observations will be discussed.
Topics: Animals; Antibodies; Antibody Formation; Antigens; Complement System Proteins; Humans; Immunoglobulin M
PubMed: 25001046
DOI: 10.1016/j.molimm.2014.06.010 -
Viruses May 2023Infectious diseases represent one of the major public health concerns on the global level [...].
Infectious diseases represent one of the major public health concerns on the global level [...].
Topics: Antibody Formation; RNA Viruses; Public Health
PubMed: 37243299
DOI: 10.3390/v15051214