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PLoS Pathogens Aug 2020
Topics: Antibodies, Neutralizing; Antibody Formation; Antigen-Antibody Complex; Autoantigens; Host-Pathogen Interactions; Humans; Immunity, Cellular; Ribonucleoproteins
PubMed: 32760166
DOI: 10.1371/journal.ppat.1008657 -
Frontiers in Immunology 2023The humoral response is frequently dysfunctioning in autoimmunity with a frequent rise in total serum immunoglobulins, among which are found autoantibodies that may be... (Review)
Review
The humoral response is frequently dysfunctioning in autoimmunity with a frequent rise in total serum immunoglobulins, among which are found autoantibodies that may be pathogenic by themselves and/or propagate the inflammatory reaction. The infiltration of autoimmune tissues by antibody-secreting cells (ASCs) constitutes another dysfunction. The known high dependency of ASCs on the microenvironment to survive combined to the high diversity of infiltrated tissues implies that ASCs must adapt. Some tissues even within a single clinical autoimmune entity are devoid of infiltration. The latter means that either the tissue is not permissive or ASCs fail to adapt. The origin of infiltrated ASCs is also variable. Indeed, ASCs may be commonly generated in the secondary lymphoid organ draining the autoimmune tissue, and home at the inflammation site under the guidance of specific chemokines. Alternatively, ASCs may be generated locally, when ectopic germinal centers are formed in the autoimmune tissue. Alloimmune tissues with the example of kidney transplantation will also be discussed own to their high similarity with autoimmune tissues. It should also be noted that antibody production is not the only function of ASCs, since cells with regulatory functions have also been described. This article will review all the phenotypic variations indicative of tissue adaptation described so for at the level of ASC-infiltrating auto/alloimmune tissues. The aim is to potentially define tissue-specific molecular targets in ASCs to improve the specificity of future autoimmune treatments.
Topics: Antibody-Producing Cells; Autoantibodies; Antibody Formation; Autoimmunity; Chemokines
PubMed: 36895558
DOI: 10.3389/fimmu.2023.1111366 -
Current Opinion in Organ Transplantation Oct 2022In antibody-mediated allograft rejection, donor-reactive antibodies cause transplant injury in part via complement activation. New mechanistic insights indicate... (Review)
Review
PURPOSE OF REVIEW
In antibody-mediated allograft rejection, donor-reactive antibodies cause transplant injury in part via complement activation. New mechanistic insights indicate complement also modulates development of humoral immune responses. Herein we review recent data that describes how complement affects antibody formation and we discuss therapeutic implications.
RECENT FINDINGS
Extravasating T cells interacting with integrins express and activate intracellular complement that drives immune-metabolic adaptations vital for CD4 + helper cells. Marginal zone B cells can acquire intact major histocompatibility complexes from dendritic cells via complement-dependent trogocytosis for presentation to T cells. Activated B cells in germinal centers receive co-stimulatory signals from T-helper cells. These germinal center B cells undergo coordinate shifts in surface complement regulator expression that permit complement receptor signaling on the germinal center B cells required for affinity maturation. The positively selected, high-affinity B cells can differentiate into plasma cells that produce donor-HLA-reactive antibodies capable of ligating endothelial, among other, graft cells. Subsequent sublytic complement attack can stimulate endothelial cells to activate CD4 + and CD8 + T cells, promoting cellular and humoral rejection. Newly developed complement inhibitors are being tested to prevent/treat transplant rejection.
SUMMARY
The complement system influences T-cell, B-cell and endothelial-cell activation, and thereby contributes allograft injury. Emerging therapeutic strategies targeting complement activation have the potential to prevent or abrogate transplant injury and improve transplant outcomes.
Topics: Antibody Formation; Complement System Proteins; Endothelial Cells; Graft Rejection; Humans; Isoantibodies
PubMed: 35857345
DOI: 10.1097/MOT.0000000000001002 -
Frontiers in Immunology 2019Dendritic cells (DCs) facilitate cross talk between the innate and adaptive immune system. They sense and phagocytose invading pathogens, and are not only capable of... (Review)
Review
Dendritic cells (DCs) facilitate cross talk between the innate and adaptive immune system. They sense and phagocytose invading pathogens, and are not only capable of activating naïve T cells, but can also determine the polarization of T cell responses into different effector subtypes. Polarized T cells in turn have a crucial role in antibody class switching and affinity maturation, and consequently the quality of the resulting humoral immunity. Targeting vaccines to DCs thus provides a great deal of opportunities for influencing the humoral immune responses, by fine-tuning the T cell response as well as regulating antigen availability for B cells. In this review we aim to outline how different DC targeted vaccination strategies can be utilized to induce a desired humoral immune response. A range of factors, including route of vaccine administration, use of adjuvants, choice of DC subset and surface receptor to target have been reported to influence the resulting immune response and will be reviewed herein. Finally, we will discuss opportunities for designing improved vaccines and challenges with translating this knowledge into clinical or veterinary medicine.
Topics: Animals; Antibody Formation; B-Lymphocytes; Dendritic Cells; Drug Delivery Systems; Gene Rearrangement, B-Lymphocyte; Humans; Immunity, Humoral; T-Lymphocytes; Vaccination; Vaccines
PubMed: 31333661
DOI: 10.3389/fimmu.2019.01529 -
The Journal of Experimental Medicine May 2017Tissue adaptation is an intrinsic component of immune cell development, influencing both resistance to pathogens and tolerance. Chronically stimulated surfaces of the... (Review)
Review
Tissue adaptation is an intrinsic component of immune cell development, influencing both resistance to pathogens and tolerance. Chronically stimulated surfaces of the body, in particular the gut mucosa, are the major sites where immune cells traffic and reside. Their adaptation to these environments requires constant discrimination between natural stimulation coming from harmless microbiota and food, and pathogens that need to be cleared. This review will focus on the adaptation of lymphocytes to the gut mucosa, a highly specialized environment that can help us understand the plasticity of leukocytes arriving at various tissue sites and how tissue-related factors operate to shape immune cell fate and function.
Topics: Adaptation, Physiological; Animals; Antibody Formation; Humans; Immune Tolerance; Intestinal Mucosa; Lymphocytes; T-Lymphocytes, Regulatory
PubMed: 28432200
DOI: 10.1084/jem.20162014 -
Oncoimmunology 2022
Topics: Animals; Antibody Formation; Ferroptosis; Marsupialia
PubMed: 36185805
DOI: 10.1080/2162402X.2022.2127273 -
Frontiers in Immunology 2020Improving understanding of the bovine adaptive immune response would equip researchers to more efficiently design interventions against pathogens that impact upon food... (Review)
Review
Improving understanding of the bovine adaptive immune response would equip researchers to more efficiently design interventions against pathogens that impact upon food security and animal welfare. There are features of the bovine antibody response that differ substantially from other mammalian species, including the best understood models in the human and mouse. These include the ability to generate a functionally diverse immunoglobulin response despite having a fraction of the germline gene diversity that underpins this process in humans and mice, and the unique structure of a subset of immunoglobulins with "ultralong" HCDR3 domains, which are of significant interest with respect to potential therapeutics, including against human pathogens. However, a more detailed understanding of the B cell response and the production of an effective antibody response in the bovine is currently hampered by the lack of reagents for the B cell lineage. In this article we outline the current state of knowledge and capabilities with regard to B cell and antibody responses in cattle, highlight resource gaps, and summarize recent advances that have the potential to fundamentally advance our understanding of this process in the bovine host.
Topics: Animals; Antibody Formation; B-Lymphocytes; Cattle
PubMed: 32595642
DOI: 10.3389/fimmu.2020.01175 -
Transplantation Apr 2022Antibody-mediated rejection (AMR) is a major barrier to long-term graft survival following solid organ transplantation (SOT). Major histocompatibility antigens... (Review)
Review
Antibody-mediated rejection (AMR) is a major barrier to long-term graft survival following solid organ transplantation (SOT). Major histocompatibility antigens mismatched between donor and recipient are well-recognized targets of humoral alloimmunity in SOT and thought to drive most cases of AMR. In contrast, the implication of minor histocompatibility antigens (mHAs) in AMR has not been fully investigated, and their clinical relevance remains controversial. Recent technological advances, allowing for genome-wide comparisons between donors and recipients, have uncovered novel, polymorphic mHA targets with potential influence on the graft outcome following SOT. Here, we review these latest studies relating to mHAs and discuss their clinical significance.
Topics: Antibody Formation; Graft Rejection; HLA Antigens; Histocompatibility; Minor Histocompatibility Antigens; Organ Transplantation
PubMed: 34699457
DOI: 10.1097/TP.0000000000003969 -
Frontiers in Immunology 2022Antibody-mediated adaptive immunity must provide effective long-term protection with minimal adverse effects, against rapidly mutating pathogens, in a human population... (Review)
Review
Antibody-mediated adaptive immunity must provide effective long-term protection with minimal adverse effects, against rapidly mutating pathogens, in a human population with diverse ages, genetics, and immune histories. In order to grasp and leverage the complexities of the antibody response, we advocate for a mechanistic understanding of the multiscale germinal center (GC) reaction - the process by which precursor B-cells evolve high-affinity antigen-specific antibodies, forming an effector repertoire of plasma and memory cells for decades-long protection. The regulatory dynamics of B-cells within the GC are complex, and unfold across multiple interacting spatial and temporal scales. At the organism scale, over weeks to years, the antibody sequence repertoire formed by various B-cell clonal lineages modulates antibody quantity and quality over time. At the tissue and cellular scale, over hours to weeks, B-cells undergo selection spatially distributed interactions with local stroma, antigen, and helper T-cells. At the molecular scale, over seconds to days, intracellular signaling, transcriptional, and epigenetic networks modulate B-cell fates and shape their clonal lineages. We summarize our current understanding within each of these scales, and identify missing links in connecting them. We suggest that quantitative multi-scale mathematical models of B-cell and GC reaction dynamics provide predictive frameworks that can apply basic immunological knowledge to practical challenges such as rational vaccine design.
Topics: Antibody Formation; Antigens; B-Lymphocytes; Cell Communication; Germinal Center; Humans; T-Lymphocytes, Helper-Inducer
PubMed: 35603162
DOI: 10.3389/fimmu.2022.898078 -
Frontiers in Immunology 2021The re-emergence of Zika virus (ZIKV) caused widespread infections that were linked to Guillain-Barré syndrome in adults and congenital malformation in fetuses, and...
The re-emergence of Zika virus (ZIKV) caused widespread infections that were linked to Guillain-Barré syndrome in adults and congenital malformation in fetuses, and epidemiological data suggest that ZIKV infection can induce protective antibody responses. A more detailed understanding of anti-ZIKV antibody responses may lead to enhanced antibody discovery and improved vaccine designs against ZIKV and related flaviviruses. Here, we applied recently-invented library-scale antibody screening technologies to determine comprehensive functional molecular and genetic profiles of naturally elicited human anti-ZIKV antibodies in three convalescent individuals. We leveraged natively paired antibody yeast display and NGS to predict antibody cross-reactivities and coarse-grain antibody affinities, to perform in-depth immune profiling of IgM, IgG, and IgA antibody repertoires in peripheral blood, and to reveal virus maturation state-dependent antibody interactions. Repertoire-scale comparison of ZIKV VLP-specific and non-specific antibodies in the same individuals also showed that mean antibody somatic hypermutation levels were substantially influenced by donor-intrinsic characteristics. These data provide insights into antiviral antibody responses to ZIKV disease and outline systems-level strategies to track human antibody immune responses to emergent viral infections.
Topics: Antibodies, Neutralizing; Antibodies, Viral; Antibody Formation; B-Lymphocytes; Computational Biology; Flow Cytometry; High-Throughput Nucleotide Sequencing; Host-Pathogen Interactions; Humans; Neutralization Tests; Peptide Library; Zika Virus; Zika Virus Infection
PubMed: 33732238
DOI: 10.3389/fimmu.2021.615102