Talk:Lymph Node Development

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Cite this page: Hill, M.A. (2024, May 7) Embryology Lymph Node Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Lymph_Node_Development

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Note - This sub-heading shows an automated computer PubMed search using the listed sub-heading term. References appear in this list based upon the date of the actual page viewing. Therefore the list of references do not reflect any editorial selection of material based on content or relevance. In comparison, references listed on the content page and discussion page (under the publication year sub-headings) do include editorial selection based upon relevance and availability. (More? Pubmed Most Recent)


Lymph Node Embryology

<pubmed limit=5>Lymph Node Embryology</pubmed>

Lymph Node Development

<pubmed limit=5>Lymph Node Development</pubmed>

PubMed

PubMed Central Images

Pubmed Central Images - Lymph Node Development | Pubmed Central Images - Lymph Node

2014

2013

2012

The origins, function, and regulation of T follicular helper cells

J Exp Med. 2012 Jul 2;209(7):1241-53. doi: 10.1084/jem.20120994.

Ma CS, Deenick EK, Batten M, Tangye SG. Source Immunology Program, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.

Abstract

The generation of high-affinity antibodies (Abs) plays a critical role in the neutralization and clearance of pathogens and subsequent host survival after natural infection with a variety of microorganisms. Most currently available vaccines rely on the induction of long-lived protective humoral immune responses by memory B cells and plasma cells, underscoring the importance of Abs in host protection. Ab responses against most antigens (Ags) require interactions between B cells and CD4(+) T helper cells, and it is now well recognized that T follicular helper cells (Tfh) specialize in providing cognate help to B cells and are fundamentally required for the generation of T cell-dependent B cell responses. Perturbations in the development and/or function of Tfh cells can manifest as immunopathologies, such as immunodeficiency, autoimmunity, and malignancy. Unraveling the cellular and molecular requirements underlying Tfh cell formation and maintenance will help to identify molecules that could be targeted for the treatment of immunological diseases that are characterized by insufficient or excessive Ab responses.

PMID 22753927

Lymph node macrophages

J Innate Immun. 2012;4(5-6):424-36. doi: 10.1159/000337007. Epub 2012 Apr 4.

Gray EE, Cyster JG. Source Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143-0414, USA.

Abstract Lymph node (LN) macrophages have long been known for their efficient uptake of lymph-borne antigens. A convergence of studies on innate and adaptive immune responses has led to exciting recent advances in understanding their more specialized properties: presenting antigens to B cells, dendritic cells and T cells, producing trophic factors and cytokines, and, remarkably, being permissive for viral infection, a property critical for mounting anti-viral responses. LN macrophages have been traditionally divided into subsets based on their subcapsular sinus and medullary locations. Here, we classify LN macrophages into three subsets: subcapsular sinus macrophages, medullary sinus macrophages and medullary cord macrophages. We review the literature regarding the roles of these cells in innate and adaptive immune responses and requirements for their development. We also discuss challenges associated with their purification as well as the existence of additional heterogeneity among LN macrophages. Copyright © 2012 S. Karger AG, Basel.

PMID 22488251

2011

Molecular programming of B cell memory

Nat Rev Immunol. 2011 Dec 9;12(1):24-34. doi: 10.1038/nri3128.

McHeyzer-Williams M, Okitsu S, Wang N, McHeyzer-Williams L. Source Department of Immunology and Microbial Sciences, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. mcheyzer@scripps.edu

Abstract

The development of high-affinity B cell memory is regulated through three separable phases, each involving antigen recognition by specific B cells and cognate T helper cells. Initially, antigen-primed B cells require cognate T cell help to gain entry into the germinal centre pathway to memory. Once in the germinal centre, B cells with variant B cell receptors must access antigens and present them to germinal centre T helper cells to enter long-lived memory B cell compartments. Following antigen recall, memory B cells require T cell help to proliferate and differentiate into plasma cells. A recent surge of information - resulting from dynamic B cell imaging in vivo and the elucidation of T follicular helper cell programmes - has reshaped the conceptual landscape surrounding the generation of memory B cells. In this Review, we integrate this new information about each phase of antigen-specific B cell development to describe the newly unravelled molecular dynamics of memory B cell programming.

PMID 22158414

http://www.nature.com/nri/journal/v12/n1/full/nri3128.html

http://www.nature.com/nri/journal/v12/n1/fig_tab/nri3128_ft.html

2010

Ontogeny of stromal organizer cells during lymph node development

J Immunol. 2010 Apr 15;184(8):4521-30. Epub 2010 Mar 17.

Bénézech C, White A, Mader E, Serre K, Parnell S, Pfeffer K, Ware CF, Anderson G, Caamaño JH. Source School of Immunity and Infection, Institute for BioMedical Research-Medical Research Council Centre for Immune Regulation, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.

Abstract

The development of secondary lymphoid organs, such as lymph nodes (LNs), in the embryo results from the reciprocal action between lymphoid tissue inducer (LTi) cells and stromal cells. However, the initial events inducing LN anlagen formation before the LTi stromal cells cross-talk interactions take place are not fully elucidated. In this study, we show that the inguinal LN anlagen in mouse embryos developed from mesenchymal cells surrounding the lymph sacs, spherical structures of endothelial cells that bud from veins. Using inguinal and mesenteric LNs (mLNs), we provide evidence supporting a two-step maturation model for stromal cells: first, ICAM-1(-)VCAM-1(-) mesenchymal precursor cells become ICAM-1(int)VCAM-1(int) cells, in a process independent of LTi cells and lymphotoxin beta receptor (LTbetaR) signaling. The second step involves the maturation of ICAM-1(int)VCAM-1(int) cells to ICAM-1(high)VCAM-1(high) mucosal addressin cell adhesion molecule-1(+) organizer cells and depends on both LTi cells and LTbetaR. Addition of alphaLTbetaR agonist to LN organ cultures was sufficient to induce ICAM-1(int)VCAM-1(int) cells to mature. In LtbetaR(-/-) embryos, both inguinal and mLN stromal cells showed a block at the ICAM-1(int)VCAM-1(int) stage, and, contrary to inguinal LNs, mLNs persist longer and contained LTi cells, which correlated with the sustained gene expression of Il-7, Cxcl13, and, to a lesser degree, Ccl21. Taken together, these results highlight the importance of the signals and cellular interactions that induce the maturation of stromal cells and ultimately lead to the formation of lymphoid tissues.

PMID 20237296

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862734

http://www.jimmunol.org/content/184/8/4521.long

2009

Lymph sacs are not required for the initiation of lymph node formation

Vondenhoff MF, van de Pavert SA, Dillard ME, Greuter M, Goverse G, Oliver G, Mebius RE.

Development. 2009 Jan;136(1):29-34.

The lymphatic vasculature drains lymph fluid from the tissue spaces of most organs and returns it to the blood vasculature for recirculation. Before reaching the circulatory system, antigens and pathogens transported by the lymph are trapped by the lymph nodes. As proposed by Florence Sabin more than a century ago and recently validated, the mammalian lymphatic vasculature has a venous origin and is derived from primitive lymph sacs scattered along the embryonic body axis. Also as proposed by Sabin, it has been generally accepted that lymph nodes originate from those embryonic primitive lymph sacs. However, we now demonstrate that the initiation of lymph node development does not require lymph sacs. We show that lymph node formation is initiated normally in E14.5 Prox1-null mouse embryos devoid of lymph sacs and lymphatic vasculature, and in E17.5 Prox1 conditional mutant embryos, which have defective lymph sacs. However, subsequent clustering of hematopoietic cells within these developing lymph nodes is less efficient.

PMID 19060331

2008

Structure and function of rat lymph nodes

Arch Histol Cytol. 2008 Sep;71(2):69-76.

Ohtani O, Ohtani Y.

Department of Anatomy, Faculty of Medicine and Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan. osmotani@med.u-toyama.ac.jp

Abstract

The lymph node comprises a critical crossroad for encounters between antigen presenting cells, antigens from lymph, and lymphocytes recruited into lymph nodes from the blood. The node consists of spaces lined with lymphatic endothelial cells and parenchyma. The former spaces can be divided into the subcapsular sinuses, lymphatic labyrinths in the deep cortex, intermediate sinuses, and medullary sinuses. The sponge-like framework of the node parenchyma is composed of collagen fibers invested with reticular cells. The parenchyma can be divided into the cortex, deep cortex, and medullary cord. Lymphocytes migrate from the node parenchyma into the lymphatic labyrinths in the deep cortex. Close to the labyrinths are high endothelial venules (HEVs), through which circulating lymphocytes enter the node parenchyma. HEVs strongly express Aquaporin-1, suggesting that HEVs are involved in the net absorption of water, but not protein, from lymph coming through afferent lymphatics. Many LYVE-1 positive sinus reticular cells (i.e., lymphatic endothelial cells) with attached macrophages form a network within the lumen of the medullary sinuses. Fluids and migrating cells arriving at the node preferentially flow through the subcapsular sinuses, intermediate sinuses, and medullary sinuses in this order. Fluids and migrating cells may also enter the cortex through gaps in the floor of the subcapsular sinuses.

PMID 18974599

Organogenesis of lymphoid tissues

Nat Rev Immunol. 2003 Apr;3(4):292-303. Mebius RE. Source Department of Molecular Cell Biology, VU University Medical Center, v.d. Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands. r.mebius.cell@med.vu.nl Erratum in Nat Rev Immunol. 2003 Jun;3(6):509.

Abstract

The development of lymphoid organs depends on the correct expression of several molecules within a defined timeframe during ontogeny. Although this is an extremely complex process, with each secondary lymphoid tissue requiring subtly different signals, a common framework for lymphoid development is beginning to emerge. Drawing on studies of lymph nodes, Peyer's patches and nasal-associated lymphoid tissue, an integrative model of lymphoid-tissue development, involving adhesion molecules, cytokines and chemokines, which emphasizes the role of interactions between CD3-CD4+CD45+ 'inducer' cells and VCAM1+ICAM1+ stromal 'organizer' cells is presented.

PMID 12669020

1996

A developmental switch in lymphocyte homing receptor and endothelial vascular addressin expression regulates lymphocyte homing and permits CD4+ CD3- cells to colonize lymph nodes

Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):11019-24.

Mebius RE, Streeter PR, Michie S, Butcher EC, Weissman IL. Department of Pathology, Stanford University School of Medicine, CA 94305, USA.

Abstract

IN adult mice, the dominant adhesion molecules involved in homing to lymph nodes are L-selectin homing receptors on lymphocytes and the peripheral lymph node addressins on specialized high endothelial venules. Here we show that, from fetal life through the first 24 hr of life, the dominant adhesion molecules are the mucosal addressin MAdCAM-1 on lymph node high endothelial venules and its counterreceptor, the Peyer's patch homing receptor, integrin alpha 4 beta 7 on circulating cells. Before birth, 40-70% of peripheral blood leukocytes are L-selectin-positive, while only 1-2% expresses alpha 4 beta 7. However, the fetal lymph nodes preferentially attract alpha 4 beta 7-expressing cells, and this can be blocked by fetal administration of anti-MAdCAM-1 antibodies. During fetal and early neonatal life, when only MAdCAM-1 is expressed on high endothelial venules, an unusual subset of CD4 + CD3- cells, exclusively expressing alpha 4 beta 7 as homing receptors, enters the lymph nodes. Beginning 24 hr after birth a developmental switch occurs, and the peripheral node addressins are upregulated on high endothelial venules in peripheral and mesenteric lymph nodes. This switch in addressin expression facilitates tissue-selective lymphocyte migration and mediates a sequential entry of different cell populations into the lymph nodes. PMID: 8855301

1981

Vascular architecture of thymus and lymph nodes, blood vessels, transmural passage of lymphocytes, and cell-interactions

Scan Electron Microsc. 1981;(Pt 3):89-98.

Irino S, Takasugi N, Murakami T.

Abstract

Postcapillary or high-endothelial venules were preferentially distributed at the cortico-medullary junction of the thymus. In the lymph nodes these venules were located in he paracortical area between cortex and medulla. The venules in the thymus were surrounded by the so-called perivascular spaces, while those in the lymph nodes were not clearly surrounded by this space. The walls of the thymus venules were fenestrated. The reticular sheets surrounding the perivascular spaces were also fenestrated. These fenestrations facilitated the transmural passage of thymocytes through the vessels. In the lymph nodes where the venules had few fenestrations, lymphocytes in transmural passages were usually suspended between the high- endothelial cells. The macrophages were preferentially located in reticular meshes of the paracortical areas, and most of these cells were in contact with lymphocytes. This might indicate that the paracortical areas are the main interaction sites of lymph node lymphocytes and macrophages. Observations on the casted samples are also reported.

PMID: 7330596 http://www.ncbi.nlm.nih.gov/pubmed/7330596

1975

Ontogeny of human fetal lymph nodes

Am J Anat. 1975 Jan;142(1):15-27.

Bailey RP, Weiss L.

Abstract

Developing lymph nodes from 30 human embryos and fetuses with crown-rump lengths (CRL) of 18 mm (5.6 wk) to 245 mm (26 wk) were examined by light microscopy. The nodes were embedded in araldite, and the sections examined were approximately 1 mu in thickness. The development of nodes was divided into three stages: 1. the lymphatic plexus and connective tissue invagination (30 mm to 67 mm CRL); 2. the early fetal lymph node (43 mm to ,5 mm CRL); and 3. the late fetal lymph node (CRL greater than 75 mm). The lymphatic plexus was formed by connective tissue invaginations and bridges which divided a lymph sac into a meshwork of channels and spaces. Connective tissue invaginations were endothelially-lined and were surrounded by lymphatic space. Reticular cells, macrophages, and blood vessels were found in these invaginations. Early fetal lymph nodes were formed from invaginations when the cellular density and lymphocyte content increased. The lymphatic space surrounding the early node was the developing subcapsular sinus. With further development the early node became packed with lymphocytes, increasing the cellular density and size of the node. The connective tissue surrounding the subcapsular sinus condensed to form the capsule. Afferent lymphatic vessels pierced the capsule. Capillaries, veins, postcapillary venules, and occasional arteries were found in early and late nodes.

PMID: 1167215 http://www.ncbi.nlm.nih.gov/pubmed/1167215


Light and electron microscopic studies of postcapillary venules in developing human fetal lymph nodes

Am J Anat. 1975 May;143(1):43-58.

Bailey RP, Weiss L.

Abstract

Developing lymph nodes from 30 human fetuses with crownrump lengths (CRL) of 38 mm (8.7 wk) to 245 mm (26 wk) were studied by light and electron microscopy. Blood vessels that appear to be postcapillary venules (PCV) are present in nodes of 47 mm CRL and older fetuses. These venules first appear in nodes whehn the nodal population of lymphocytes is sparse. In these early nodes PCV are distributed randomly and consist of a low endothelium, underlying basal lamina and incomplete pericyte sheath. Early nodal PCV are distinguised from other nodal blood vessels by the presence of lymphocyte diapedesis and several luminal lymphocytes. In the late stages of nodal development PCV are the more common non-capillary blood vessel and appear in the parenchyma near the periphery of the node. Late nodal PCV are generally characterized by a cuboidal endothelium that is rich in Golgi apparatus, lysosomes and Weibel-Palade bodies. The lumen and wall of late nodal PCV contain lymphocytes. The relationship between the development of the parenchyma of fetal nodes and the appearance and activity of PCV, the passage of lymphocytes through the PCV wall and the fine structure of developing PCV are described. It is suggested that the lymphocytes that first appear in developing nodes, and the majority of the lymphocytes found in late nodes, migrate to the node via the blood vascular system and enter the nodal parenchyma by passing across PCV endothelium.

PMID: 165702 http://www.ncbi.nlm.nih.gov/pubmed/165702

1971

Ultrastructure of the normal lymph node.

Am J Pathol. 1971 Oct;65(1):1-24.

Nopajaroonsri C, Luk SC, Simon GT.

Abstract The "normal" lymph node has been studied by electron microscopy. The lymphoid tissue can be divided into three distinct zones. Zone 1 consists of loosely arranged cells surrounding the lymphatic sinuses and blood vessels. This is the only zone in which plasma cells are present. Zone 2 is surrounded by zone 1 and consists of compactly arranged cells in which lymphocytes predominate. Zone 3 (germinal center) appears only after antigenic stimulation. It is characterized by large, ribosome-rich cells and macrophages containing phagocytosed lymphocytes. These zones are arranged with their longest diameters pointing towards the hilus. Zone 1 is the longest and extends across the cortex, paracortex and medulla. Zone 2 spans across cortex and paracortex. Zone 3 usually is confined to the cortex. Our preliminary studies indicate that zone 1 is mainly bursal dependent, zone 2 is mainly thymic dependent and zone 3 is bursal dependent.

PMID: 5096365

Immunobiology Textbook

Immunobiology 5th edition The Immune System in Health and Disease Charles A Janeway, Jr, Paul Travers, Mark Walport, and Mark J Shlomchik.

Part I. An Introduction to Immunobiology and Innate Immunity

Part III. The Development of Mature Lymphocyte Receptor Repertoires


Links: Blue Histology - Lymph Nodes

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