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Perpetual expression of PAMPs necessary for optimal immune control and clearance of a persistent pathogen
Pathogen-associated molecular patterns are involved in the initiation of anti-pathogen immunity but their importance for sustaining this response is not established. Here, the authors show that persistent presence of pathogen-associated molecular patterns is required to maintain robust immune responses to pathogens.
- Samarchith P. Kurup
- & Rick L. Tarleton
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| Open AccessQuantal and graded stimulation of B lymphocytes as alternative strategies for regulating adaptive immune responses
B lymphocytes respond to stimulation by proliferating and differentiating. Here the authors quantify and model the responses of B lymphocytes to TLR and CD40-dependent stimulation, and find that the latter induces a more complex response to signals of varying strength.
- E.D. Hawkins
- , M.L. Turner
- & P.D. Hodgkin
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Highly self-reactive naive CD4 T cells are prone to differentiate into regulatory T cells
The differentiation of naive CD4 T cells into T-helper-cell subsets is thought to be influenced by factors in the T-cell environment. Martin et al.reveal that cell intrinsic differences also determine lineage commitment and show that cells with the highest avidity for self are most likely to become induced regulatory T cells.
- Bruno Martin
- , Cédric Auffray
- & Bruno Lucas
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| Open AccessExploring the MHC-peptide matrix of central tolerance in the human thymus
T cells learn to tolerate self-antigens in the thymus, where self-peptides are presented by thymic antigen-presenting cells. Here, the authors present an ex vivomass spectrometric analysis of the self-peptide repertoire associated with MHC I and II in human thymic tissue.
- Eleni Adamopoulou
- , Stefan Tenzer
- & Christina Stoeckle
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B7-H5 costimulates human T cells via CD28H
The end-result of stimulation of T-cell receptors by antigen is in part determined by co-signalling pathways such as the B7/CD28 axis. Zhu et al.identify a novel costimulatory CD28-like receptor and ligand pathway in human T cells.
- Yuwen Zhu
- , Sheng Yao
- & Lieping Chen
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| Open AccessGANP regulates recruitment of AID to immunoglobulin variable regions by modulating transcription and nucleosome occupancy
The affinity of antibodies for their targets is enhanced by somatic hypermutation, in which the cytidine deaminase AID is recruited to immunoglobulin variable region genes in B cells. Here the authors show that the nuclear protein GANP has an important role in this process by modifying chromatin structure and enhancing AID recruitment.
- Shailendra Kumar Singh
- , Kazuhiko Maeda
- & Nobuo Sakaguchi
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Regulation of asymmetric cell division and polarity by Scribble is not required for humoral immunity
B cells are thought to divide asymmetrically to generate distinct lineages required for adaptive immunity. Hawkins et al. find that surprisingly, mice lacking components of a complex required for asymmetric cell division display normal responses to vaccination and viral infection.
- Edwin D. Hawkins
- , Jane Oliaro
- & Sarah M. Russell
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| Open AccessBasophils are required for the induction of Th2 immunity to haptens and peptide antigens
Both dendritic cells and basophils have been shown to influence T helper 2 cell induction, however the relative importance of their roles remains unclear. Otsuka et al. find that basophils present hapten and peptide antigens to T cells, but are unable to present protein antigens in the absence of dendritic cells.
- Atsushi Otsuka
- , Saeko Nakajima
- & Kenji Kabashima
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| Open AccessMicrobe-dependent CD11b+ IgA+ plasma cells mediate robust early-phase intestinal IgA responses in mice
Intestinal plasma cells contribute to the delicate balance between immunity against pathogens and tolerance of intestinal microflora. Kunisawa et al. identify a subpopulation of plasma cells whose proliferation depends on stimulation by microbes and IL-10, and which mediate early-phase responses to oral antigens.
- Jun Kunisawa
- , Masashi Gohda
- & Hiroshi Kiyono
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| Open AccessProstaglandin E2 promotes Th1 differentiation via synergistic amplification of IL-12 signalling by cAMP and PI3-kinase
Activation of cAMP signalling by prostaglandin E2 (PGE2) has long been thought to suppress Tcell receptor activation and Th1 cell differentiation. Yao et al. reveal that dual stimulation of both cAMP and PI 3-kinase pathways by PGE2 synergistically promotes Th1 differentiation by amplifying IL-12 and IFN-γsignalling.
- Chengcan Yao
- , Takako Hirata
- & Shuh Narumiya
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Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation
The human germinal centre-associated lymphoma gene is expressed in germinal centre B-lymphocytes; however, its function is unknown. Here the authors show that human germinal centre-associated lymphoma activates Syk kinase, leading to lymphoid hyperplasia and systemic reactive amyloid A amyloidosis in transgenic mice.
- Isabel Romero-Camarero
- , Xiaoyu Jiang
- & Izidore S Lossos
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Extensive diversification of IgH subclass-encoding genes and IgM subclass switching in crocodilians
Different mechanisms for generating antibody diversity have evolved since the emergence of immunoglobulin genes in jawed vertebrates. By sequencing the crocodilian immunoglobulin heavy-chain locus, Chenget al. uncover new insights into the evolutionary origins of adaptive immunity.
- Gang Cheng
- , Yang Gao
- & Yaofeng Zhao
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| Open AccessT-bet and GATA3 orchestrate Th1 and Th2 differentiation through lineage-specific targeting of distal regulatory elements
T-bet and GATA3 regulate differentiation of T cells into Th1 or Th2 cell fates, but little is known about their functional interaction outside of the IFNγ and Il4 /Il5/Il13 loci. Kanhere et al. map these factors across the genome in human T cells, revealing unappreciated breadth of function and interplay between them.
- Aditi Kanhere
- , Arnulf Hertweck
- & Richard G. Jenner
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Identification and characterization of polyclonal αβ-T cells with dendritic cell properties
The division of the immune system into innate and adaptive arms has become blurred in recent years. Kuka et al.identify a novel population of αβ-T-cell receptor-expressing cells in mice and humans that both presents and responds to antigen and produces interleukin-12, thus exhibiting core properties of both dendritic cells and T cells.
- Mirela Kuka
- , Ivana Munitic
- & Jonathan D. Ashwell
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| Open AccessFoxP3+ regulatory CD4 T cells control the generation of functional CD8 memory
The role of CD4+ T cells in the generation of memory CD8+ T cells is not fully understood. In this study, the exposure of CD8 memory precursors to interleukin-2 during early antigen priming is shown to be controlled by FoxP3+ regulatory CD4+T cells, resulting in the production of functional memory cells.
- M.G. de Goër de Herve
- , S. Jaafoura
- & Y. Taoufik
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The CD4+ T-cell help signal is transmitted from APC to CD8+ T-cells via CD27–CD70 interactions
CD8+ memory cytotoxic T lymphocytes need help from CD4+ T cells to undergo secondary expansion but the mechanisms of help are not fully understood. Here, it is shown that, after activation by CD4+ T cells, antigen-presenting cells activate CD8+T cells via the CD70/CD27 co-stimulatory pathway.
- Sonia Feau
- , Zacarias Garcia
- & Stephen P. Schoenberger
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| Open AccessMolecular memory of prior infections activates the CRISPR/Cas adaptive bacterial immunity system
The clustered regularly interspaced short palindromic repeats (CRISPR) system protects prokaryotes from foreign DNA. Here, bacteriophage DNA containing mutations that can circumvent this response are shown to be incorporated into the CRISPR locus, allowing bacteria to remember previous infections in an adaptive manner.
- Kirill A. Datsenko
- , Ksenia Pougach
- & Ekaterina Semenova
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| Open AccessBCR-signalling synergizes with TLR-signalling for induction of AID and immunoglobulin class-switching through the non-canonical NF-κB pathway
Class switch recombination diversifies antibody effector functions and requires expression of activation-induced cytidine deaminase (AID). In this study, ligation of the B-cell receptor and Toll-like receptors synergize to induce non-canonical NF-κB activation, AID expression and class switching recombination.
- Egest J. Pone
- , Jinsong Zhang
- & Paolo Casali
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| Open AccessCompetition for FcRn-mediated transport gives rise to short half-life of human IgG3 and offers therapeutic potential
The half-life of IgG is regulated by binding to the neonatal Fc receptor and, in the case of IgG3, is reduced compared to other IgG proteins. In this study, a mutation in IgG3 is shown to reduce binding to the neonatal Fc receptor, which can be competitively blocked by IgG1.
- Nigel M. Stapleton
- , Jan Terje Andersen
- & Gestur Vidarsson
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In-vitro derived germinal centre B cells differentially generate memory B or plasma cells in vivo
In response to antigens, B cells proliferate and form germinal centres before differentiating into memory B cells or long-lived plasma cells. Here, a culture method is used to expand B cells in vitro, with the ability to shift the fate of the cells between memory B cells and long-lived plasma cells.
- Takuya Nojima
- , Kei Haniuda
- & Daisuke Kitamura
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| Open AccessTranscription factor IRF8 directs a silencing programme for TH17 cell differentiation
The molecular mechanisms that regulate TH17 cell diversity are poorly understood. Ouyang et al. show that the transcription factor interferon regulatory factor-8 is required for TH17-cell differentiation and that its absence increases the severity of an experimental model of colitis.
- Xinshou Ouyang
- , Ruihua Zhang
- & Huabao Xiong
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| Open AccessProstaglandin E2 and SOCS1 have a role in intestinal immune tolerance
The gut is populated by a myriad of microorganisms and how the immune system tolerates their presence is of great interest. Here, by studying colon morphology in multiple knockout mice, the authors demonstrate a potential role for prostaglandin E2 and SOCS1 in mediating immune tolerance.
- Takatoshi Chinen
- , Kyoko Komai
- & Akihiko Yoshimura
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The structure of superantigen complexed with TCR and MHC reveals novel insights into superantigenic T cell activation
Superantigens are bacterial toxins that interact with host immunoreceptors. Salineet al.report the X-ray structure of staphylococcal enterotoxin H in complex with its human receptors, MHC class II and the T-cell receptor, providing new insights into superantigenic T-cell activation.
- Maria Saline
- , Karin E. J. Rödström
- & Karin Lindkvist-Petersson
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| Open AccessB-cell depletion reveals a role for antibodies in the control of chronic HIV-1 infection
HIV infection can be partially regulated by the host immune system; however whether B cells contribute to this response is unclear. Huanget al. show that transient depletion of B cells can result in an increase in HIV viral load suggesting that these immune cells do participate in the control of HIV infection.
- Kuan-Hsiang G. Huang
- , David Bonsall
- & Paul Klenerman