A chemokine-driven positive feedback loop organizes lymphoid follicles

K. Mark Ansel, Vu N. Ngo, Paul L. Hyman, Sanjiv A. Luther, Reinhold Förster, Jonathon D. Sedgwick, Jeffrey L. Browning, Martin Lipp and Jason G. Cyster ()
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K. Mark Ansel: Department of Microbiology and Immunology University of California San Francisco
Vu N. Ngo: Department of Microbiology and Immunology University of California San Francisco
Paul L. Hyman: Department of Microbiology and Immunology University of California San Francisco
Sanjiv A. Luther: Department of Microbiology and Immunology University of California San Francisco
Reinhold Förster: Molecular Tumorgenetics and Immunogenetics, Max-Delbrück-Center for Molecular Medicine
Jonathon D. Sedgwick: DNAX Research Institute
Jeffrey L. Browning: Biogen Inc.
Martin Lipp: Molecular Tumorgenetics and Immunogenetics, Max-Delbrück-Center for Molecular Medicine
Jason G. Cyster: Department of Microbiology and Immunology University of California San Francisco

Nature, 2000, vol. 406, issue 6793, 309-314

Abstract: 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 follicles1, 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)2,3 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 upregulate membrane lymphotoxin α1β2, a cytokine that promotes follicular dendritic cell development and BLC expression4,5, 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.

Date: 2000
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DOI: 10.1038/35018581

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