Abstract
The factors directing marginal zone B cells to the splenic marginal zone are not well understood. Here we report that FTY720, a drug that targets sphingosine 1-phosphate (S1P) receptors, induced marginal zone B cell migration into follicles. Marginal zone B cells expressed S1P receptors 1 and 3 (S1P(1) and S1P(3), respectively). Using gene-targeted mice, we show that S1P(1) but not S1P(3) was required for localization in the marginal zone. In mice lacking the chemokine CXCL13, S1P(1)-deficient marginal zone B cells reacquired a marginal zone distribution. Exposure to lipopolysaccharide or antigen caused marginal zone B cells to downregulate S1P(1) and S1P(3) and to migrate into the splenic white pulp. These data suggest that marginal zone B cell localization to the marginal zone depends on responsiveness to the blood lysophospholipid S1P, with S1P(1) signaling overcoming the recruiting activity of CXCL13.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens / pharmacology
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B-Lymphocytes / cytology*
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B-Lymphocytes / drug effects
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism*
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Cell Movement* / drug effects
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Chemokine CXCL13
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Chemokines, CXC / deficiency
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Chemokines, CXC / genetics
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Chimera / immunology
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Down-Regulation / drug effects
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Fingolimod Hydrochloride
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Flow Cytometry
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Immunohistochemistry
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Lipopolysaccharides / pharmacology
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Liver / cytology
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Liver / embryology
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Liver / metabolism
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Mice
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Mice, Transgenic
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Propylene Glycols / pharmacology
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Receptors, G-Protein-Coupled / agonists
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Receptors, G-Protein-Coupled / deficiency
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Receptors, G-Protein-Coupled / genetics
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Receptors, G-Protein-Coupled / metabolism*
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Receptors, Lysophospholipid
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Sphingosine / analogs & derivatives
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Spleen / cytology*
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Spleen / immunology
Substances
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Antigens
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Chemokine CXCL13
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Chemokines, CXC
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Cxcl13 protein, mouse
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Lipopolysaccharides
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Propylene Glycols
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Receptors, G-Protein-Coupled
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Receptors, Lysophospholipid
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Fingolimod Hydrochloride
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Sphingosine