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Sphingosine 1-phosphate regulates peritoneal B cell trafficking for subsequent intestinal IgA production

Blood 109:3749-3756, 2007
Jun Kunisawa1,2, Yosuke Kurashima1,2, Masashi Gohda1,2, Morio Higuchi1,2, Izumi Ishikawa1,2, Fumi Miura1,2, Ikuko Ogahara1,2, and Hiroshi Kiyono1,2
1: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo
2: Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation (JST)

Secretory IgA (S-IgA) is a hallmark antibody principally produced at mucosal sites and plays an important role in the creation of immunological surveillance and homeostasis at mucosa. In addition to the IgA induction through gut-associated lymphoid tissues (e.g., Peyer’s patch), peritoneal B cells have been considered to be another source of S-IgA, especially specific for the T-independent antigen. Here we show that the trafficking of peritoneal B cells is principally regulated by sphingosine 1-phosphate (S1P). Peritoneal B cells expressed high levels of the type 1 S1P receptor. Thus, disruption of S1P-mediated signaling caused a rapid disappearance of peritoneal B cells. These changes did not affect natural plasma antibody production or phosphorylcholine (PC)-specific antibody production in serum after peritoneal immunization with heat-killed streptococcal pneumoniae. However, it dramatically reduced peritoneal B cell-derived natural intestinal S-IgA production without affecting the expression of J-chain and poly Ig receptors. Additionally, PC-specific fecal IgA responses after oral immunization with R36A were significantly impaired. These findings point to a pivotal role for S1P in connecting peritoneal B cells with intestinal B cell immunity.