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The sphingosine-1-phosphate (S1P) lysophospholipid receptor S1P3 regulates MAdCAM-1+ endothelial cells in splenic marginal sinus organization

Academic Article
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Overview

authors

  • Girkontaite, I.
  • Sakk, V.
  • Wagner, M.
  • Borggrefe, T.
  • Tedford, K.
  • Chun, Jerold
  • Fischer, K. D.

publication date

  • December 2004

journal

  • Journal of Experimental Medicine  Journal

abstract

  • Marginal zones (MZs) are microdomains in the spleen that contain various types of immune cells, including MZ B cells, MOMA1(+) metallophilic macrophages, and mucosal addressin cell adhesion molecule 1 (MAdCAM-1)(+) endothelial cells. MAdCAM-1(+) and MOMA1(+) cells line the sinus, that separates MZs from splenic follicles. Here we show that a receptor for the lysophospholipid sphingosine-1-phosphate (S1P), S1P(3), is required for normal numbers of splenic immature and MZ B cells, and for S1P-induced chemotaxis of MZ B cells. S1P(3) is also essential for proper alignment of MOMA1(+) macrophages and MAdCAM-1(+) endothelial cells along the marginal sinus. The lack of cohesion of the marginal sinus in S1P(3)(-/-) mice affects MZ B cell functions, as wild-type (WT) MZ B cells migrate more into S1P(3)(-/-) follicles than into WT follicles after treatment with lipopolysaccharide. Additionally, short-term homing experiments demonstrate that WT MZ B cells home to the S1P(3)(-/-) spleen in increased numbers, suggesting a role for the marginal sinus in regulating MZ B cells numbers. Moreover, S1P(3)(-/-) mice are defective in mounting immune responses to thymus-independent antigen type 2 due to defects in radiation-resistant cells in the spleen. These data identify lysophospholipids and the S1P(3) receptor as essential regulators of the MZ sinus and its role as a barrier to the follicle.

subject areas

  • Animals
  • B-Lymphocytes
  • Cell Adhesion Molecules
  • Cell Movement
  • Endothelial Cells
  • Immunoglobulins
  • Lipopolysaccharides
  • Macrophages
  • Mice
  • Mice, Inbred C57BL
  • Mucoproteins
  • Receptors, Lysosphingolipid
  • Spleen
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Research

keywords

  • B cells
  • MOMA1(divided by) metallophilic macrophages
  • endothelium
  • lipopolysaccharide
  • marginal zone
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Identity

PubMed Central ID

  • PMC2211946

International Standard Serial Number (ISSN)

  • 0022-1007

Digital Object Identifier (DOI)

  • 10.1084/jem.20041483

PubMed ID

  • 15583019
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Additional Document Info

start page

  • 1491

end page

  • 1501

volume

  • 200

issue

  • 11

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