The extracellular matrix of the spleen as a potential organizer of immune cell compartments (original) (raw)
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Extracellular matrix of secondary lymphoid organs impacts on B-cell fate and survival
Proceedings of the National Academy of Sciences, 2013
We describe a unique extracellular matrix (ECM) niche in the spleen, the marginal zone (MZ), characterized by the basement membrane glycoproteins, laminin α5 and agrin, that promotes formation of a specialized population of MZ B lymphocytes that respond rapidly to blood-borne antigens. Mice with reduced laminin α5 expression show reduced MZ B cells and increased numbers of newly formed (NF) transitional B cells that migrate from the bone marrow, without changes in other immune or stromal cell compartments. Transient integrin α6β1-mediated interaction of NF B cells with laminin α5 in the MZ supports the MZ B-cell population, their long-term survival, and antibody response. Data suggest that the unique 3D structure and biochemical composition of the ECM of lymphoid organs impacts on immune cell fate.
Extracellular matrix of lymphoid tissues in the chick
Journal of Histochemistry & Cytochemistry, 1989
We describe the immunohistochemical distribution of components of the extracellular matrix of the chick lymphoid system. In the thymus, basement membranes of epithelial cells bordering the lobules were intensely stained by laminin antibodies; fibronectin antibodies labeled the capsule and the septal matrix, and similar reactivity was seen with tropoelastin and gp 115 antibodies. No positivity was detected with any of the antibodies within the cortical parenchymal cells. Laminin was not detected in the medullary parenchyma, whereas fibronectin was present as coarse fibers. Tropoelastin and gp 115 appeared as a finer and more diffuse meshwork. In the bursa, laminin antibodies outlined the epithelial cells separating the cortex from the medulla. Fibronectin, tropoelastin, and gp 115 antibody stained the interfollicular septa and the cortical matrix, although to a different extent. Laminin was also detected in association with the interfollicular epithelium (IFE) basement membrane, wher...
Immunophenotypic analysis of human spleen compartments
Annals of Anatomy - Anatomischer Anzeiger, 2002
Microanatomical compartments of the human spleen are yet under evaluation as most of the present information comes from experiments on animals with different anatomical structures. Immune staining of stromal and blood-born cells by cell surface antigens facilitates the differentiation of functional microanatomical compartmentalization of immune organs, including the spleen. Twenty-two specimens from healthy adult subjects with the average age of 35.6+ 13.8 (Range 17 to 58) years were included in this study. Monoclonal antibodies used in this study were supplied from the 5 th, 6 th and 7 th International Workshops and Conferences on Human Leukocyte Differentiation Antigens. Tetraspan antigens presented a rather unique staining pattern in the human spleen, suggesting special roles for each (CD9, CD53, CD63, CD151 and CD231) in certain locations. Sinus lining cells presented a distinctive antigenic profile, sharing both endothelial cell (CD31, CD36, CD54, CD62R CD102, CD105, CD106 and CD146) and macrophage lineage characteristics. The sheathed capillaries were not restricted to the perifollicular zone alone. Extracellular matrix receptors (CD49 a, CD49 b, CD49 c, CD49 e, CD49f, CD29 and CD44) stained the penicillary arterioles and vascular smooth muscle. These molecules were also found on the vascular endothelium. Leukocyte antigens (CD11a, CD11b, CD22, CD43, CD45, CD45RB, CD45RO and CD50) were mainly expressed in the white and red pulp of the spleen at different intensities, excluding the penicillary arterioles. Activation antigens (CD26, CD71 and CD98) presented a diffuse and broad staining pattern. In conclusion, microanatomical compartmentalization, microcirculation and function of the human spleen were evaluated using a wide panel of monoclonal antibodies.
Spleen in innate and adaptive immunity regulation
AIMS Allergy and Immunology
The spleen is a large secondary lymphoid organ located in the bloodstream , primarily functioning as a massive blood filter. It filtered effete red blood cells, antigen-antibody complexes, apoptotic bodies, damaged cells, among others. Spleen's myriad microanatomy reflects the diversity and complexity of its functions. As a specialized immune organ, the spleen immune system plays a significant role in innate and adaptive immunity. Specialized innate immune cells like B cells, natural killer (NK) cells, and macrophages populate locations within the spleen. Specifically, the spleen is a crucial organ for peripheral immune tolerance, complementing central immune tolerance. Spleen remains the only organ in the body capable of mounting an appropriate immune response to encapsulated bacteria. Spleen houses tolerogenic immune cells like CD8 + Treg cells, F4/80 + macrophages, CD68 + F4/80 + red pulp macrophages, CD169 + metallophillic macrophages, CD8 + CD205 + splenic dendritic cells (DCs), splenic CD8α + CD103 + CD207 + DCs, CD43 +ve CD19 hi CD5 +ve IgM hi IgD lo B cells, and splenic NKT cells that express regulated on activation normal T cell expressed and secreted (RANTES/CCL5) chemokine. Splenocytes are extra-thymic autoimmune regulator gene (AIRE) expressing cells that regulate tissue-specific antigens' expression to confer peripheral immune tolerance. As such, the spleen provides the right site for counteracting autoimmunity. Splenectomy in both study animals and humans results in overwhelming infections with, especially encapsulated bacteria. The anterior chamber-associated immune deviation (ACAID) is closely related to the spleen that needs to be studied to improve transplant survival. The role of the spleen in anti-tumor immunity yields an inconclusive result. In-depth research is needed to find which cells or pathways are linked to favorable outcomes concerning cancer. Understanding the spleen's microanatomy and physiology will provide a 2
Organizer-Like Reticular Stromal Cell Layer Common to Adult Secondary Lymphoid Organs
The Journal of Immunology, 2008
Supplementary ml http://www.jimmunol.org/content/suppl/2008/10/17/181.9.6189.DC1.ht References http://www.jimmunol.org/content/181/9/6189.full#ref-list-1 , 23 of which you can access for free at: cites 57 articles This article Subscriptions http://jimmunol.org/subscriptions is online at: The Journal of Immunology Information about subscribing to
Differential Expression of Basement Membrane Components in Lymphatic Tissues
Journal of Histochemistry and Cytochemistry, 2004
Peripheral lymphoid tissues act as important organs of immunological defense. Characteristic of their architecture is the rich reticular fiber meshwork composed of various extracellular matrix (ECM) molecules with which the stationary non-lymphatic cells stay in intimate contact and form channels through which the lymphatic cells travel. Here we studied the distribution of various laminin (Ln) chains and different types of collagens in human spleen, lymph node, and tonsil to clarify their chain-specific distribution. The most widely distributed proteins in all these organs were Ln chains alpha5, beta1, gamma1 and collagen types IV and XVIII, which were present in practically all compartments. Conversely, Ln alpha1, alpha2, alpha4, and type VII collagen showed a more restricted expression pattern. A unique feature was that Ln alpha3-, beta3-, and gamma2-chains, which normally are not localized to the vascular wall in non-lymphatic tissues, were present also in capillary basement membranes (BMs) of the follicular structures of lymph node and tonsil and in Ln alpha1-chain and type VII collagen also in the splenic white pulp. We also found that collagen XVII was exclusively present in the ring fibers of the spleen. The results indicate that BMs of lymphatic tissues contain a variety of macromolecules that probably contribute strongly to immunological events. In addition, capillaries of the lymphoid tissue exhibit a specified BM composition resembling that in epithelial BMs of non-lymphoid tissues.
Function of CD4+CD3- cells in relation to B- and T-zone stroma in spleen
Blood, 2007
␣-deficient mice, which lack segregation of their B-and T-cell areas, acquire normal organization following adoptive transfer into RAG-deficient recipients, identifying a non-B non-T cell in the segregation process. Here we show that a CD4 ؉ CD3 ؊ accessory cell is tightly associated with discrete VCAM-1-expressing stromal cells in B-and T-cell areas of the mouse spleen. CD4 ؉ CD3 ؊ cells express high levels of LT␣, LT, and tumor necrosis factor (TNF) ␣, which are the ligands for the LT receptor and TNFR1 expressed by stromal cells. The expression of these ligands is functional, as transferring CD4 ؉ CD3 ؊ cells derived from either embryonic or adult tissues into LT␣deficient mice organizes B/T segregation and up-regulates CCL21 protein expres-sion in areas where T cells are segregated from B cells. We propose that the function of CD4 ؉ CD3 ؊ cells is to form a link between primed CD4 T cells and the underlying stromal elements, creating distinct microenvironments in which they enable effector responses. (Blood. 2007;
BMC Immunology, 2010
Background: The lymph node (LN) is a crossroads of blood and lymphatic vessels allowing circulating lymphocytes to efficiently recognize foreign molecules displayed on antigen presenting cells. Increasing evidence indicates that after crossing high endothelial venules, lymphocytes migrate within the node along the reticular network (RN), a scaffold of fibers enwrapped by fibroblastic reticular cells (FRC). Light microscopy has shown that the RN contains specific extracellular matrix (ECM) proteins, which are putative molecular "footholds" for migration, and are known ligands for lymphocyte integrin adhesion receptors. Results: To investigate whether ECM proteins of the RN are present on the outer surface of the FRC and are thus accessible to migrating lymphocytes, ultrastructural immunohistochemical staining of cynomolgus monkey LN was performed using antibodies to human ECM proteins that were successfully employed at the light microscopic level. The fibrillar collagens I and III were observed primarily within the reticular network fibers themselves. In contrast, the matrix proteins laminin, fibronectin, collagen IV, and tenascin were observed within the reticular fibers and also on the outer membrane surface of the FRC.