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Blood, 1 May 2008, Vol. 111, No. 9, pp. 4646-4652. Prepublished online as a Blood First Edition Paper on February 21, 2008; DOI 10.1182/blood-2007-10-120071. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-10-120071v1 111/9/4646    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kunisawa, J. Articles by Kiyono, H. Search for Related Content PubMed PubMed Citation Articles by Kunisawa, J. Articles by Kiyono, H. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Sphingosine 1-phosphate–dependent trafficking of peritoneal B cells requires functional NFB-inducing kinase in stromal cells Jun Kunisawa*,13, Masashi Gohda*,1,2, Yosuke Kurashima1,4, Izumi Ishikawa1,3, Morio Higuchi1,4, and Hiroshi Kiyono14 1 Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Tokyo; 2 Department of Medical Genome Science, Graduate School of Frontier Science, University of Tokyo, Tokyo; 3 Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation (JST), Saitama; and 4 Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Tokyo, Japan We previously reported that sphingosine 1-phosphate (S1P) regulates peritoneal B-cell trafficking and subsequent intestinal IgA production, but the underlying mechanisms remain obscure. We demonstrate here that nuclear factor B–inducing kinase (NIK) is involved in the regulation of S1P-mediated trafficking of peritoneal B cells. Although peritoneal B cells from NIK-mutated alymphoplasia (aly) mice expressed type 1 S1P receptor (S1P1) at comparable levels and demonstrated normal migration toward S1P, aly peritoneal B cells showed decreased sensitivity to FTY720, an S1P1 modulator. NIK-mutated stromal cells showed decreased levels of adhesion molecules (VCAM-1 and ICAM-1) and increased CXCL13 expressions, leading to impaired ability to support S1P-mediated emigration, but not immigration, of peritoneal B cells. Therefore, aly peritoneal B cells exhibited normal S1P-mediated peritoneal B-cell trafficking from peritoneum to intestine for IgA production when they were transferred into severe combined immunodeficient or wild-type mice. However, S1P-mediated emigration of wild-type B cells from the aly peritoneal cavity was impaired without affecting their immigration from the blood. Further, transfer of wild-type stromal cells into the peritoneum restored S1P-mediated trafficking of aly peritoneal B cells. These findings suggest that NIK in stromal cells has a specific role in the regulation of S1P-mediated trafficking of peritoneal B cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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