Immunological Reviews最新文献

{"title":"Activation of Anergic B Cells During Development of Autoimmunity.","authors":"Mohammad Mansoor, Brandon K Hilliard, Mia J Smith","doi":"10.1111/imr.70175","DOIUrl":"https://doi.org/10.1111/imr.70175","url":null,"abstract":"<p><p>In healthy individuals, autoreactive B cells are normally silenced via central and peripheral tolerance mechanisms. In the periphery, when autoreactive B cells recognize self-antigen via their B cell receptor (BCR) (signal 1) but do not receive T cell help (signal 2), they undergo the tolerance mechanism called anergy. Human anergic B cells are termed B_ND (Naïve IgD+ B cells). Previous studies have shown that B_ND cells are decreased in the peripheral blood of individuals with autoimmunity, suggesting they may have become activated and contributed to the development of disease. In line with this, recently it has been found that a portion of the remaining anergic B cells present in the blood of autoimmune individuals exhibit an activated phenotype. In this review, we will summarize what is known and unknown about these cells, including their relation to other recognized autoreactive B cell subsets, how they become activated in the first place, and what their pathogenic functions are. Understanding how B_ND cells break tolerance and contribute to disease will advance the development of new therapeutic approaches and highlight novel cell populations amenable to depletion.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"342 1","pages":"e70175"},"PeriodicalIF":10.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148899845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural T-Cell Receptor Analysis in the Age of Machine Learning.","authors":"Nele P Quast, Matthew I J Raybould, Charlotte M Deane","doi":"10.1111/imr.70168","DOIUrl":"https://doi.org/10.1111/imr.70168","url":null,"abstract":"<p><p>The development of highly accurate deep learning models for protein structure prediction has transformed the landscape of T-cell receptor (TCR) structure data, which can now be accessed at repertoire scale. We provide a perspective on the growing field of structural TCR immunoinformatics, summarizing core principles of TCR structural biology and highlighting existing resources and tools. We outline computational methods for TCR structure prediction, and discuss outstanding challenges faced by current tools, as well as potential avenues to address these. We expand on the research enabled by the availability of predicted TCR structures, exploring the utility of TCR structure predictions for computationally inferring TCR specificity, as well as summarizing opportunities emerging from the adjacent field of antibody research. Finally, we provide a forward-looking perspective on the advances in deep learning research which have recently enabled computational design of TCRs and TCR-like binders.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"342 1","pages":"e70168"},"PeriodicalIF":10.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Germinal Center Selection and Plasma Cell Differentiation.","authors":"Adrien Sprumont, Oliver Bannard","doi":"10.1111/imr.70169","DOIUrl":"10.1111/imr.70169","url":null,"abstract":"<p><p>Germinal centers (GCs) are specialized microenvironments in which B cells undergo affinity maturation through iterative cycles of somatic hypermutation, proliferation and selection, generating antibodies with improved antigen-binding properties. Although GC B cells do not themselves secrete antibody, they differentiate into memory B cells and plasma cells that provide long-term humoral immunity. GC selection has traditionally been viewed as a process that preferentially expands B cells expressing the highest-affinity B cell receptors. However, recent studies have revealed that physiological GC responses preserve substantial clonal and affinity diversity, and generate plasma cells spanning a broad range of antibody affinities. Here, we review current understanding of the mechanisms governing GC B cell selection and discuss an alternative framework in which T cell help quantitatively refuels GC B cells rather than acting as a binary gate for cyclic re-entry. We further explore how antigen organization, antibody feedback and the biophysical context of antigen recognition may reconcile the apparent discrepancy between affinity-based selection and the maintenance of clonal diversity. Finally, we consider how these concepts may alter our expectations for the plasma cell populations emerging from GCs and discuss their implications for rational vaccine design.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"342 1","pages":"e70169"},"PeriodicalIF":10.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping the Altered Landscape of TCR Repertoire in Autoimmune Diseases.","authors":"Celine Albalaa, Martin Pezous, David Klatzmann, Encarnita Mariotti-Ferrandiz","doi":"10.1111/imr.70174","DOIUrl":"10.1111/imr.70174","url":null,"abstract":"<p><p>Autoimmune diseases arise from the breakdown of immune tolerance through complex interactions between genetic predisposition, environmental exposures, and adaptive immune responses. High-throughput T-cell receptor (TCR) repertoire sequencing has transformed our ability to characterize these responses, providing unprecedented insights into clonal dynamics, antigen-driven selection, and immune history. In this review, we summarize the major alterations of TCR repertoires reported across autoimmune diseases, including changes in diversity, clonal expansion, repertoire architecture, and tissue distribution. We discuss the principal biological and technical challenges that currently limit repertoire interpretation, with particular emphasis on the concept that bulk repertoires represent composite mixtures of biologically distinct T-cell populations. Finally, we highlight emerging approaches integrating single-cell profiling, computational modeling, and antigen-specificity inference that are reshaping the field. We propose that TCR repertoires should be viewed as dynamic molecular footprints of autoimmune disease, providing a systems-level framework to improve mechanistic understanding, biomarker discovery, and the development of precision immunotherapies.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"342 1","pages":"e70174"},"PeriodicalIF":10.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Cell Selection and Migration in the Establishment of Long-Lived Antibody Responses.","authors":"Wataru Ise, Kazuhiro Suzuki, Tomohiro Kurosaki","doi":"10.1111/imr.70173","DOIUrl":"10.1111/imr.70173","url":null,"abstract":"<p><p>As B cells are activated and differentiate into plasma cells, they execute migration programs that allow them to traffic within secondary lymphoid tissues and reach the bone marrow, where they can mature as long-lived plasma cells. Recent studies have revealed mechanisms underlying not only affinity-driven but also isotype-driven plasma cell selection. In addition, the importance of migration programs in plasma cell longevity has become increasingly appreciated. This review focuses on mechanisms that regulate plasma cell numbers and their migration to the bone marrow, with emphasis on our findings and recent advances in related fields.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"342 1","pages":"e70173"},"PeriodicalIF":10.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective and Pathogenic Antibodies to Citrullinated Antigens","authors":"Outi Sareila,&nbsp;Yibo He,&nbsp;Zhongwei Xu,&nbsp;Changrong Ge,&nbsp;Erik Lönnblom,&nbsp;Rikard Holmdahl","doi":"10.1111/imr.70165","DOIUrl":"10.1111/imr.70165","url":null,"abstract":"<p>Autoimmune diseases start years before clinical onset. In rheumatoid arthritis (RA), autoantibodies to citrullinated proteins (ACPA) and to modified IgG (rheumatoid factors, RF) can be detected many years before the inflammatory attack on cartilaginous joints. It has been assumed that these antibodies are pathogenic. We show here that many of the antibodies produced before disease onset are protective although there are likely also pathogenic clones directed to cartilaginous joints. To determine the function of these antibodies, it is crucial to analyze them in vivo, which is only possible in mouse models. To ease the translation, we have genetically humanized models which will now allow a more accurate analysis of autoimmune mechanisms in human disease. In this review, we will also discuss what we know today regarding the targeted epitopes and the role of pathogenic and protective antibodies. With this knowledge as the basis, we have developed new types of serologic tests for RA.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"342 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70165","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Some Exposure for Influenza Hemagglutinin Interface Antibodies","authors":"Kevin R. McCarthy","doi":"10.1111/imr.70167","DOIUrl":"https://doi.org/10.1111/imr.70167","url":null,"abstract":"<p>Influenza viruses are a constant threat to human health. Current vaccines often confer low to moderate protection against infection with seasonal viruses and little-to-no protection against pandemic viruses. Improved vaccines are needed. These vaccines will need to reliably elicit antibodies to conserved sites that are broadly protective. One strategy to do so is to design immunogens that present epitopes that are targeted by antibodies that are genetically similar, that humans have the genetic capacity to produce, and that are likely present in human naive B cell repertoires. Among the more recently described epitopes for broadly binding, protective antibodies are those on surfaces at protein–protein interfaces. This review will focus on describing many of these sites and the genetic features of antibodies that engage them. Interface epitopes are immunogenic, and antibodies to these sites are likely present in human repertoires following influenza infection or vaccination.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"342 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70167","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interferon-Mediated Regulation of Memory B Cell Identity and Function","authors":"Alana Kirn,&nbsp;Kim L. Good-Jacobson","doi":"10.1111/imr.70161","DOIUrl":"https://doi.org/10.1111/imr.70161","url":null,"abstract":"<p>Memory B cells are essential for long-lasting immunity induced by both encountered pathogens and vaccines. Functional diversity within the memory B cell pool is established through interactions between memory B cells and the environment in which they develop and reside. This review will discuss novel insights into the role of cytokines encountered in the microenvironment in modulating memory B cell transcriptomic, epigenetic, and phenotypic identity. Specifically, it will focus on how interferons can prime unique memory B cell subpopulations upregulated in chronic viral infection, autoimmunity, and cancer. Understanding how memory B cell identity is established and maintained in interferon-primed memory B cell subsets, and how memory B cell phenotype relates to function, may help advise novel vaccine design and diagnostic procedures for a wide range of immunopathologies.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"341 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70161","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of the T Cell Receptor Sequence in Shaping T Cell Functional Fate","authors":"Sreekar Mantena,&nbsp;Soumya Raychaudhuri","doi":"10.1111/imr.70157","DOIUrl":"https://doi.org/10.1111/imr.70157","url":null,"abstract":"<div>\u0000 \u0000 <p>The T cell receptor (TCR) has long been studied through the lens of antigen recognition, with decades of work characterizing how the TCR sequence specifies the peptide–MHC ligands a T cell can engage. Yet a growing body of evidence indicates that the TCR sequence carries another dimension of functional information: it biases the transcriptional fate a T cell is likely to adopt. In this review, we synthesize the evidence that TCR sequence features shape T cell differentiation during both thymic development and peripheral responses. We provide an overview of the landscape of T cell fates and the TCR structure, describe advancements in technologies to profile T cell phenotype and TCR sequence, and outline computational strategies for modeling the relationship between them. We specifically examine four reproducible axes of covariation between TCR sequence and T cell fate, including innate-like lineages, regulatory T cells, CD4 versus CD8 commitment, and peripheral memory formation. Understanding the probabilistic fate biases encoded by the TCR may advance our ability to interpret repertoires in health and disease and engineer next-generation cellular therapies.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"341 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardio-Immunology: Reframing the Pathogenesis of Cardiovascular Disease","authors":"Douglas L. Mann","doi":"10.1111/imr.70163","DOIUrl":"https://doi.org/10.1111/imr.70163","url":null,"abstract":"&lt;p&gt;For decades, cardiovascular disease was understood primarily through metabolic, hemodynamic, and structural models that linked hypercholesterolemia and hypertension to vascular disease, atherosclerotic plaque formation, ischemic injury, cardiac hypertrophy, and ultimately to the development of heart failure. Over the past 15 years, our understanding of cardiovascular disease pathogenesis has undergone a major conceptual shift, with dysregulated innate and adaptive immune responses now recognized as central features of major cardiovascular disorders, including atherosclerotic coronary artery disease, vascular disease, hypertension, and heart failure (Figure 1). The Cardio-Immunology compendium in this issue of &lt;i&gt;Immunological Reviews&lt;/i&gt; brings together sixteen comprehensive reviews, written by experts and pioneers in their fields that collectively map the immune mechanisms that maintain cardiovascular homeostasis and drive cardiovascular disease, laying the groundwork for precision immune-targeted therapeutics that have the potential to transform cardiovascular care.&lt;/p&gt;&lt;p&gt;A deeper understanding of the role of inflammation in the heart begins with its evolutionary role in preserving tissue homeostasis. In the opening contribution, Mann reframes the relationship between phylogenetically ancient immune responses and myocardial injury through the lens of disease tolerance: A cell-autonomous stress-response program that coordinates cytoprotective signaling in cardiac myocytes with tightly regulated, self-limited inflammatory responses after tissue injury, mediated in part by trained innate immunity [&lt;span&gt;1&lt;/span&gt;]. A central insight highlighted in this article, and a recurrent theme throughout the compendium, is that inflammation is not inherently pathological; rather, its salutary effects become maladaptive when inflammatory responses are dysregulated, excessive, or sustained.&lt;/p&gt;&lt;p&gt;Aging has long been recognized as the strongest risk factor for developing cardiovascular disease; however, therapies that directly target cardiovascular aging remain limited. Zanders, Dimmeler, and colleagues synthesize evidence implicating cellular senescence and the senescence-associated secretory phenotype (SASP) as drivers of inflammaging, chronic low-grade inflammation coupled to vascular and cardiac remodeling [&lt;span&gt;2&lt;/span&gt;]. Senescent cells accumulate in aging cardiovascular tissue, secrete pro-inflammatory mediators, including IL-6, IL-8, TNF, and MMP-3, activate immune cells, and impair tissue repair. Senolytics, SASP modulators, anti-inflammatory agents, and metabolic interventions such as metformin show promise, but translating senescence biology into therapies that improve cardiovascular outcomes in older adults remains an unmet need. Studying immune niches within the myocardium offers another framework for understanding aging-related cardiac dysfunction. Perez-Shibayana, Ludewig, and colleagues describe how immune cells cooperate with fibroblast and ","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"341 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.70163","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}