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A chemokine-driven positive feedback loop organizes lymphoid follicles

Item Type:Article
Title:A chemokine-driven positive feedback loop organizes lymphoid follicles
Creators Name:Ansel, K.M. and Ngo, V.N. and Hyman, P.L. and Luther, S.A. and Foerster, R. and Sedgwick, J.D. and Browning, J.L. and Lipp, M. and Cyster, J.G.
Abstract:Lymphoid follicles are B-cell-rich compartments of lymphoid organs that function as sites of B-cell antigen encounter and differentiation. CXC chemokine receptor-5 (CXCR5) is required for B-cell migration to splenic follicles, but the requirements for homing to B-cell areas in lymph nodes remain to be defined. Here we show that lymph nodes contain two types of B- cell-rich compartment: follicles containing follicular dendritic cells, and areas lacking such cells. Using gene-targeted mice, we establish that B- lymphocyte chemoattractant (BLC/BCA1) and its receptor, CXCR5, are needed for B-cell homing to follicles in lymph nodes as well as in spleen. We also find that BLC is required for the development of most lymph nodes and Peyer's patches. In addition to mediating chemoattraction, BLC induces B cells to up- regulate membrane lymphotoxin α1β2, a cytokine that promotes follicular dendritic cell development and BLC expression establishing a positive feedback loop that is likely to be important in follicle development and homeostasis. In germinal centres the feedback loop is overridden, with B-cell lymphotoxin α1β2 expression being induced by a mechanism independent of BLC.
Keywords:B-Lymphocytes, Cell Differentiation, Chemokine Receptors, Cultured Cells, Cytokine Receptors, CXC Chemokines, Dendritic Cells, Feedback, Lymph Nodes, Lymphotoxin-Alpha, Peyers Patches, Animals, Mice
Source:Nature
ISSN:0028-0836
Publisher:Nature Publishing Group (U.K.)
Volume:406
Number:6793
Page Range:309-314
Date:20 July 2000
Official Publication:https://doi.org/10.1038/35018581
PubMed:View item in PubMed

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