Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 203, Issue 12, Pages 2683-2690Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20061289
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Funding
- NIAID NIH HHS [R01 AI045073, N01AI40098, AI45073] Funding Source: Medline
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After induction in secondary lymphoid organs, a subset of antibody-secreting cells (ASCs) homes to the bone marrow (BM) and contributes to long-term antibody production. The factors determining secondary lymphoid organ residence versus BM tropism have been unclear. Here we demonstrate that in mice treated with FTY720 or that lack sphingosine-1-phosphate (S1P) receptor-1 (S1P(1)) in B cells, IgG ASCs are induced and localize normally in secondary lymphoid organs but they are reduced in numbers in blood and BM. Many IgG ASCs home to BM on day 3 of the secondary response and day 3 splenic ASCs exhibit S1P responsiveness, whereas the cells remaining at day 5 are unable to respond. S1P(1) mRNA abundance is higher in ASCs isolated from blood compared to spleen, whereas CXCR4 expression is lower. Blood ASCs also express higher amounts of Kruppel-like factor (KLF)2, a regulator of S1P(1) gene expression. These findings establish an essential role for S1P(1) in IgG plasma cell homing and they suggest that differential regulation of S1P(1) expression in differentiating plasma cells may determine whether they remain in secondary lymphoid organs or home to BM.
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