Submitted October 24, 2007
Accepted February 6, 2008
Sphingosine 1-phosphate-dependent trafficking of peritoneal B cells requires functional NF
B-inducing kinase in stromal cells
Jun Kunisawa, Masashi Gohda, Yosuke Kurashima, Izumi Ishikawa, Morio Higuchi, and Hiroshi Kiyono*
Department of Microbiology and Immunology, Division of Mucosal Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Department of Medical Genome Science, Graduate School of Frontier Science, The University of Tokyo, Tokyo, Japan
Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan
Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation (JST), Tokyo, Japan
* Corresponding author; email: kiyono{at}ims.u-tokyo.ac.jp.
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 the 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 SCID 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.
