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Cold Spring Harbor Perspectives in Biology

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https://www.readbyqxmd.com/read/28630079/what-are-the-primary-limitations-in-b-cell-affinity-maturation-and-how-much-affinity-maturation-can-we-drive-with-vaccination-lessons-from-the-antibody-response-to-hiv-1
#1
Gabriel D Victora, Hugo Mouquet
Most broadly neutralizing antibodies to HIV-1 have in common an extreme degree of somatic hypermutation (SHM), which correlates with their ability to neutralize multiple viral strains. However, achieving such extreme SHM by immunization remains a challenge. Here, we discuss how antigenic variation during HIV-1 infection may work to exacerbate SHM by permitting multiple iterative cycles of affinity maturation in germinal centers, and speculate on how this could be recapitulated through vaccination.
June 19, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28630078/what-are-the-primary-limitations-in-b-cell-affinity-maturation-and-how-much-affinity-maturation-can-we-drive-with-vaccination-a-role-for-antibody-feedback
#2
Kai-Michael Toellner, Daniel M-Y Sze, Yang Zhang
We discuss the impact of antibody feedback on affinity maturation of B cells. Competition from epitope-specific antibodies produced earlier during the immune response leads to immune complex formation, which is essential for transport and deposition of antigen onto follicular dendritic cells (FDCs). It also reduces the concentration of free epitopes into the μm to nm range, which is essential for B-cell receptors (BCRs) to sense affinity-dependent changes in binding capacity. Antibody feedback may also induce epitope spreading, leading to a broader selection of epitopes recognized by newly emerging B-cell clones...
June 19, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28630077/what-are-the-primary-limitations-in-b-cell-affinity-maturation-and-how-much-affinity-maturation-can-we-drive-with-vaccination-breaking-through-immunity-s-glass-ceiling
#3
Garnett Kelsoe, Barton F Haynes
A key goal of HIV-1 vaccine development is the induction of broadly neutralizing antibodies (bnAbs) targeted to the vulnerable regions of the HIV envelope. BnAbs develop over time in ∼50% of HIV-1-infected individuals. However, to date, no vaccines have induced bnAbs and few or none of these vaccine-elicited HIV-1 antibodies carry the high frequencies of V(D)J mutations characteristic of bnAbs. Do the high frequencies of mutations characteristic of naturally induced bnAbs represent a fundamental barrier to the induction of bnAbs by vaccines? Recent studies suggest that high frequencies of V(D)J mutations can be achieved by serial vaccination strategies...
June 19, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28630076/what-are-the-primary-limitations-in-b-cell-affinity-maturation-and-how-much-affinity-maturation-can-we-drive-with-vaccination-is-affinity-maturation-a-self-defeating-process-for-eliciting-broad-protection
#4
Christopher T Stamper, Patrick C Wilson
Vaccinations are one of the greatest success stories of modern medicine, saving millions of lives since their widespread adoption. However, several diseases continue to elude highly effective vaccination strategies. Chief among these are human immunodeficiency virus (HIV) and influenza (flu), both of which will require vaccines that can guide the creation of highly mutated, broadly neutralizing antibodies (bnAbs). The generation of bnAbs is hindered by our inability to effectively drive the high levels of affinity maturation required to achieve them in a large number of cells...
June 19, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28620098/cytokine-signaling-in-the-development-and-homeostasis-of-regulatory-t-cells
#5
Kevin H Toomer, Thomas R Malek
Cytokine signaling is indispensable for regulatory T-cell (Treg) development in the thymus, and also influences the homeostasis, phenotypic diversity, and function of Tregs in the periphery. Because Tregs are required for establishment and maintenance of immunological self-tolerance, investigating the role of cytokines in Treg biology carries therapeutic potential in the context of autoimmune disease. This review discusses the potent and diverse influences of interleukin (IL)-2 signaling on the Treg compartment, an area of knowledge that has led to the use of low-dose IL-2 as a therapy to reregulate autoaggressive immune responses...
June 15, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28620097/interleukin-17-family-cytokines-signaling-mechanisms-biological-activities-and-therapeutic-implications
#6
Leticia Monin, Sarah L Gaffen
The cytokines of the interleukin 17 (IL-17) family play a central role in the control of infections, especially extracellular fungi. Conversely, if unrestrained, these inflammatory cytokines contribute to the pathology of numerous autoimmune and chronic inflammatory conditions. Recent advances have led to the approval of IL-17A-blocking biologics for the treatment of moderate to severe plaque psoriasis, but much remains to be understood about the biological functions, regulation, and signaling pathways downstream of these factors...
June 15, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28620096/interleukin-6-family-cytokines
#7
Stefan Rose-John
The interleukin (IL)-6 family cytokines is a group of cytokines consisting of IL-6, IL-11, ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), oncostatin M (OSM), cardiotrophin 1 (CT-1), cardiotrophin-like cytokine (CLC), and IL-27. They are grouped into one family because the receptor complex of each cytokine contains two (IL-6 and IL-11) or one molecule (all others cytokines) of the signaling receptor subunit gp130. IL-6 family cytokines have overlapping but also distinct biologic activities and are involved among others in the regulation of the hepatic acute phase reaction, in B-cell stimulation, in the regulation of the balance between regulatory and effector T cells, in metabolic regulation, and in many neural functions...
June 15, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28620095/responses-to-cytokines-and-interferons-that-depend-upon-jaks-and-stats
#8
George R Stark, HyeonJoo Cheon, Yuxin Wang
Many cytokines and all interferons activate members of a small family of kinases (the Janus kinases [JAKs]) and a slightly larger family of transcription factors (the signal transducers and activators of transcription [STATs]), which are essential components of pathways that induce the expression of specific sets of genes in susceptible cells. JAK-STAT pathways are required for many innate and acquired immune responses, and the activities of these pathways must be finely regulated to avoid major immune dysfunctions...
June 15, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28600396/a-50-year-personal-journey-location-gene-expression-and-circadian-rhythms
#9
Michael Rosbash
I worked almost exclusively on nucleic acids and gene expression from the age of 19 as an undergraduate until the age of 38 as an associate professor. Mentors featured prominently in my choice of paths. My friendship with influential Brandeis colleagues then persuaded me that genetics was an important tool for studying gene expression, and I switched my experimental organism to yeast for this reason. Several years later, friendship also played a prominent role in my beginning work on circadian rhythms. As luck would have it, gene expression as well as genetics turned out to be important for circadian timekeeping...
June 9, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28600395/cell-cell-junctions-organize-structural-and-signaling-networks
#10
Miguel A Garcia, W James Nelson, Natalie Chavez
Cell-cell junctions link cells to each other in tissues, and regulate tissue homeostasis in critical cell processes that include tissue barrier function, cell proliferation, and migration. Defects in cell-cell junctions give rise to a wide range of tissue abnormalities that disrupt homeostasis and are common in genetic abnormalities and cancers. Here, we discuss the organization and function of cell-cell junctions primarily involved in adhesion (tight junction, adherens junction, and desmosomes) in two different epithelial tissues: a simple epithelium (intestine) and a stratified epithelium (epidermis)...
June 9, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28600394/tgf-%C3%AE-family-signaling-in-early-vertebrate-development
#11
Joseph Zinski, Benjamin Tajer, Mary C Mullins
TGF-β family ligands function in inducing and patterning many tissues of the early vertebrate embryonic body plan. Nodal signaling is essential for the specification of mesendodermal tissues and the concurrent cellular movements of gastrulation. Bone morphogenetic protein (BMP) signaling patterns tissues along the dorsal-ventral axis and simultaneously directs the cell movements of convergence and extension. After gastrulation, a second wave of Nodal signaling breaks the symmetry between the left and right sides of the embryo...
June 9, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28600393/cell-junctions-in-hippo-signaling
#12
Ruchan Karaman, Georg Halder
The Hippo signal transduction pathway is an important regulator of organ growth and cell differentiation, and its deregulation contributes to the development of cancer. The activity of the Hippo pathway is strongly dependent on cell junctions, cellular architecture, and the mechanical properties of the microenvironment. In this review, we discuss recent advances in our understanding of how cell junctions transduce signals from the microenvironment and control the activity of the Hippo pathway. We also discuss how these mechanisms may control organ growth during development and regeneration, and how defects in them deregulate Hippo signaling in cancer cells...
June 9, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28507022/loss-of-e-cadherin-dependent-cell-cell-adhesion-and-the-development-and-progression-of-cancer
#13
Heather C Bruner, Patrick W B Derksen
Classical cadherins are the key molecules that control cell-cell adhesion. Notwithstanding this function, it is also clear that classical cadherins are more than just the "glue" that keeps the cells together. Cadherins are essential regulators of tissue homeostasis that govern multiple facets of cellular function and development, by transducing adhesive signals to a complex network of signaling effectors and transcriptional programs. In cancer, cadherins are often inactivated or functionally inhibited, resulting in disease development and/or progression...
May 15, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28507021/cell-biology-of-tight-junction-barrier-regulation-and-mucosal-disease
#14
Aaron Buckley, Jerrold R Turner
Mucosal surfaces are lined by epithelial cells. In the intestine, the epithelium establishes a selectively permeable barrier that supports nutrient absorption and waste secretion while preventing intrusion by luminal materials. Intestinal epithelia therefore play a central role in regulating interactions between the mucosal immune system and luminal contents, which include dietary antigens, a diverse intestinal microbiome, and pathogens. The paracellular space is sealed by the tight junction, which is maintained by a complex network of protein interactions...
May 15, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28507020/tgf-%C3%AE-family-signaling-in-mesenchymal-differentiation
#15
Ingo Grafe, Stefanie Alexander, Jonathan R Peterson, Taylor Nicholas Snider, Benjamin Levi, Brendan Lee, Yuji Mishina
Mesenchymal stem cells (MSCs) can differentiate into several lineages during development and also contribute to tissue homeostasis and regeneration, although the requirements for both may be distinct. MSC lineage commitment and progression in differentiation are regulated by members of the transforming growth factor-β (TGF-β) family. This review focuses on the roles of TGF-β family signaling in mesenchymal lineage commitment and differentiation into osteoblasts, chondrocytes, myoblasts, adipocytes, and tenocytes...
May 15, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28432135/molecular-mechanisms-of-sleep-homeostasis-in-flies-and-mammals
#16
Ravi Allada, Chiara Cirelli, Amita Sehgal
Sleep is homeostatically regulated with sleep pressure accumulating with the increasing duration of prior wakefulness. Yet, a clear understanding of the molecular components of the homeostat, as well as the molecular and cellular processes they sense and control to regulate sleep intensity and duration, remain a mystery. Here, we will discuss the cellular and molecular basis of sleep homeostasis, first focusing on the best homeostatic sleep marker in vertebrates, slow wave activity; second, moving to the molecular genetic analysis of sleep homeostasis in the fruit fly Drosophila; and, finally, discussing more systemic aspects of sleep homeostasis...
April 21, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28432134/tgf-%C3%AE-1-signaling-and-tissue-fibrosis
#17
Kevin K Kim, Dean Sheppard, Harold A Chapman
Activation of TGF-β1 initiates a program of temporary collagen accumulation important to wound repair in many organs. However, the outcome of temporary extracellular matrix strengthening all too frequently morphs into progressive fibrosis, contributing to morbidity and mortality worldwide. To avoid this maladaptive outcome, TGF-β1 signaling is regulated at numerous levels and intimately connected to feedback signals that limit accumulation. Here, we examine the current understanding of the core functions of TGF-β1 in promoting collagen accumulation, parallel pathways that promote physiological repair, and pathological triggers that tip the balance toward progressive fibrosis...
April 21, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28432133/do-memory-cd4-t-cells-keep-their-cell-type-programming-plasticity-versus-fate-commitment-t-cell-heterogeneity-plasticity-and-selection-in-humans
#18
Federica Sallusto, Antonino Cassotta, Daniel Hoces, Mathilde Foglierini, Antonio Lanzavecchia
The wide range of effector and memory T cells is instrumental for immune regulation and tailored mechanisms of protection against pathogens. Here, we will focus on human CD4 T cells and discuss T-cell plasticity and intraclonal diversification in the context of a progressive and selective model of CD4 T-cell differentiation.
April 21, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28432132/do-memory-cd4-t-cells-keep-their-cell-type-programming-plasticity-versus-fate-commitment-epigenome-a-dynamic-vehicle-for-transmitting-and-recording-cytokine-signaling
#19
John L Johnson, Golnaz Vahedi
CD4(+) T cells are critical for the elimination of an immense array of microbial pathogens. Although there are aspects of helper T-cell differentiation that can be modeled as a classic cell-fate commitment, CD4(+) T cells also maintain considerable flexibility in their transcriptional program. Here, we present an overview of chromatin biology during cellular reprogramming and, within this context, envision how the scope of cellular reprogramming may be expanded to further our understanding of the controversy surrounding CD4(+) T lymphocyte plasticity or determinism...
April 21, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28432131/do-the-microbiota-influence-vaccines-and-protective-immunity-to-pathogens-if-so-is-there-potential-for-efficacious-microbiota-based-vaccines
#20
Dan R Littman
The gut-resident constituents of the microbiota protect the mucosa from invasive pathogens through engagement of both innate and adaptive branches of the immune system. They are also likely to provide systemic protection from pathogens, by enhancing host robustness and tolerance to the invasive microbes and by inducing immune responses that prevent their growth. These properties of commensal microbiota, particularly the capacity of some bacteria to induce diverse types of antigen-specific immune responses, raises the prospect that they could be deployed as vaccine vectors to generate effective local and systemic immunity to viral and bacterial pathogens...
April 21, 2017: Cold Spring Harbor Perspectives in Biology
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