The sphingosine-1-phosphate (S1P) lysophospholipid receptor S1P3 regulates MAdCAM-1+ endothelial cells in splenic marginal sinus organization.
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.
Girkontaite
Irute
I
Department of Physiological Chemistry, University of Ulm, Albert-Einstein-Allee 11, D-89069 Ulm, Germany.
Sakk
Vadim
V
Wagner
Martin
M
Borggrefe
Tilman
T
Tedford
Kerry
K
Chun
Jerold
J
Fischer
Klaus-Dieter
KD
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D015815:Cell Adhesion Molecules; D002465:Cell Movement; D042783:Endothelial Cells / Q000502:physiology*; D007136:Immunoglobulins / Q000032:analysis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009088:Mucoproteins / Q000032:analysis*; D049349:Receptors, Lysosphingolipid / Q000502:physiology*; D013154:Spleen / Q000166:cytology*
D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D008070:Lipopolysaccharides; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D049349:Receptors, Lysosphingolipid