Plasma cell S1P(1) expression determines secondary lymphoid organ retention versus bone marrow tropism
Details
Publication Year 2006-11-27, Volume 203, Issue #12, Page 2683-2690
Journal Title
JOURNAL OF EXPERIMENTAL MEDICINE
Publication Type
Journal Article
Abstract
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.
Publisher
ROCKEFELLER UNIV PRESS
Keywords
SPHINGOSINE 1-PHOSPHATE RECEPTORS; ANTIBODY-PRODUCTION; IMMUNE-RESPONSE; T-CELLS; B-CELLS; HUMORAL IMMUNITY; DENDRITIC CELLS; SPHINGOSINE-1-PHOSPHATE; MEMORY; RESPONSIVENESS
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2006-11-27 12:00:00
Last Modified: 0001-01-01 12:00:00
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