Integrin-mediated long-term B cell retention in the splenic marginal zone.
The mechanisms that control localization of marginal zone (MZ) B cells are poorly understood. Here we show that MZ B cells express elevated levels of the integrins LFA-1 (alphaLbeta2) and alpha4beta1 and that they bind to the ligands ICAM-1 and VCAM-1. These ligands are expressed within the MZ in a lymphotoxin-dependent manner. Combined inhibition of LFA-1 and alpha4beta1 causes a rapid and selective release of B cells from the MZ. Furthermore, lipopolysaccharide-triggered MZ B cell relocalization involves down-regulation of integrin-mediated adhesion. These studies identify key requirements for MZ B cell localization and establish a role for integrins in peripheral lymphoid tissue compartmentalization.
Lu
Theresa T
TT
Howard Hughes Medical Institute, Department of Microbiology and Immunology, University of California, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
Cyster
Jason G
JG
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002448:Cell Adhesion; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte; D039041:Integrin alpha4beta1; D016023:Integrins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D018655:Lymphocyte Count; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D008233:Lymphotoxin-alpha / Q000502:physiology; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D016201:Receptors, Lymphocyte Homing / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D013154:Spleen / Q000166:cytology* / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism
D054382:Chemokine CXCL13; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse; D039041:Integrin alpha4beta1; D016023:Integrins; D008024:Ligands; D008070:Lipopolysaccharides; D016169:Lymphocyte Function-Associated Antigen-1; D008233:Lymphotoxin-alpha; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1