Lymph node B lymphocyte trafficking is constrained by anatomy and highly dependent upon chemoattractant desensitization

B lymphocyte recirculation through lymph nodes (LNs) requires crossing endothelial barriers and chemoattractant-triggered cell migration. Here we show how LN anatomy and chemoattractant receptor signaling organize B lymphocyte LN trafficking. Blood-borne B cells predominately used CCR7 signaling to...

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Veröffentlicht in:Blood 2012-01, Vol.119 (4), p.978-989
Hauptverfasser: Park, Chung, Hwang, Il-Young, Sinha, Rajesh K., Kamenyeva, Olena, Davis, Michael D., Kehrl, John H.
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container_end_page 989
container_issue 4
container_start_page 978
container_title Blood
container_volume 119
creator Park, Chung
Hwang, Il-Young
Sinha, Rajesh K.
Kamenyeva, Olena
Davis, Michael D.
Kehrl, John H.
description B lymphocyte recirculation through lymph nodes (LNs) requires crossing endothelial barriers and chemoattractant-triggered cell migration. Here we show how LN anatomy and chemoattractant receptor signaling organize B lymphocyte LN trafficking. Blood-borne B cells predominately used CCR7 signaling to adhere to high endothelial venules (HEVs). New B cell emigrants slowly transited the HEV perivenule space, and thereafter localized nearby, avoiding the follicle. Eventually, the newly arrived B cells entered the basal portion of the follicle gradually populating it. In contrast, newly arriving activated B cells rapidly crossed HEVs and migrated toward the lymph node follicle. During their LN residency, recirculating B cells reacquired their sphingosine-1 phospate receptor 1 (S1P1) receptors and markedly attenuated their sensitivity to chemokines. Eventually, the B cells exited the LN follicle by entering the cortical lymphatics or returning to the paracortical cords. Upon entering the lymph, the B cells lost their polarity, down-regulated their S1P1 receptors, and subsequently strongly up-regulated their sensitivity to chemokines. These results are summarized in a model of homeostatic trafficking of B cells through LNs.
doi_str_mv 10.1182/blood-2011-06-364273
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subjects Animals
B-Lymphocytes - cytology
B-Lymphocytes - immunology
B-Lymphocytes - metabolism
Biological and medical sciences
Cell Adhesion
Cells, Cultured
Chemokines - metabolism
Chemotaxis, Leukocyte
Crosses, Genetic
Down-Regulation
Groin
Hematologic and hematopoietic diseases
Immunobiology
Kinetics
Lymph Nodes - anatomy & histology
Lymph Nodes - cytology
Lymph Nodes - immunology
Lymph Nodes - metabolism
Lymphatic System - anatomy & histology
Lymphatic System - cytology
Lymphatic System - immunology
Lymphatic System - metabolism
Medical sciences
Mice
Mice, Inbred C57BL
Mice, Transgenic
Models, Biological
Receptors, CCR7 - metabolism
Receptors, Chemokine - metabolism
Receptors, Lysosphingolipid - metabolism
Signal Transduction
Transendothelial and Transepithelial Migration
title Lymph node B lymphocyte trafficking is constrained by anatomy and highly dependent upon chemoattractant desensitization
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