Abstract
Abstract Our previous study showed that sphingosine 1-phosphate (S1P) regulates peritoneal B cell trafficking for the subsequent intestinal IgA production. In this study, we demonstrate that stromal NFkappaB-inducing kinase (NIK) is specifically involved in this pathway. Although peritoneal B cells from NIK-mutated alymphoplasia (aly) mice expressed substantial levels of S1P receptor and showed normal migration toward S1P, aly peritoneal B cells showed decreased sensitivity to FTY720, an S1P modulator. NIK-mutated stromal cells showed aberrant expression of VCAM-1, ICAM-1, and CXCL13, leading to the impaired ability to support S1P-mediated peritoneal B cell emigration. Therefore, aly peritoneal B cells exhibited normal S1P-mediated peritoneal B cell trafficking from peritoneum to intestine for IgA production when they were adoptively transferred into SCID mice. 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 peritoneal B cell-derived intestinal IgA production. This work was supported by grants from the Ministry of Education, Science, Sports, and Culture of Japan and the Ministry of Health and Welfare of Japan.
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