The Journal of Experimental Medicine
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Published online 13 November 2006 doi:10.1084/jem.20061289
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 12, 2683-2690
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ARTICLE

 Plasma cell S1P1 expression determines secondary lymphoid organ retention versus bone marrow tropism

Kenji Kabashima1, Nicole M. Haynes1, Ying Xu1, Stephen L. Nutt2, Maria L. Allende3, Richard L. Proia3, and Jason G. Cyster1

1 Howard Hughes Medical Institute (HHMI) and Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143
2 The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3050, Australia
3 Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892

CORRESPONDENCE Jason G. Cyster: Jason.Cyster{at}ucsf.edu

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 (S1P1) 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. S1P1 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 S1P1 gene expression. These findings establish an essential role for S1P1 in IgG plasma cell homing and they suggest that differential regulation of S1P1 expression in differentiating plasma cells may determine whether they remain in secondary lymphoid organs or home to BM.

Abbreviations used: ASC, antibody-secreting cell; KLF, Kruppel-like factor; NP-CGG, 4-hydroxy-3-nitrophenyl-acetyl coupled to chicken {gamma}-globulin; PC, plasma cell; RP, red-pulp; S1P, sphingosine-1-phosphate; S1P1, S1P receptor-1; SRBC, sheep red blood cell.

K. Kabashima and N. Haynes contributed equally to this work.

K. Kabashima's present address is Department of Dermatology, University of Environmental and Occupational Health, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan.


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