The Journal of Experimental Medicine
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Published 3 February 2003. doi:10.1084/jem.20021569
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© Rockefeller University Press, 0022-1007/2003/2/353 $5.00
The Journal of Experimental Medicine, Volume 197, Number 3, 353-361

Integrin-dependence of Lymphocyte Entry into the Splenic White Pulp

Charles G. Lo1, Theresa T. Lu1,2 and Jason G. Cyster1

1 Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143
2 Division of Pediatric Immunology and Rheumatology, University of California San Francisco, San Francisco, CA 94143

Address correspondence to Jason G. Cyster, Department of Microbiology and Immunology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143. Phone: 415-502-6427; Fax: 415-502-8424; E-mail: cyster{at}itsa.ucsf.edu

The steps involved in lymphocyte homing to the white pulp cords of the spleen are poorly understood. We demonstrate here that the integrins lymphocyte function associated (LFA)-1 and {alpha}4ß1 make essential and mostly overlapping contributions necessary for B cell migration into white pulp cords. T cell entry to the white pulp is also reduced by blockade of LFA-1 and {alpha}4ß1. The LFA-1 ligand, intercellular adhesion molecule 1 is critical for lymphocyte entry and both hematopoietic cells and radiation-resistant cells contribute to this requirement. Vascular cell adhesion molecule 1 contributes to the {alpha}4ß1 ligand requirement and a second ligand, possibly fibronectin, also plays a role. By contrast with the entry requirements, antigen-induced movement of B cells from follicles to the outer T zone is not prevented by integrin blocking antibodies. Comparison of the distribution of integrin-blocked B cells and B cells treated with the G{alpha}i inhibitor, pertussis toxin, early after transfer reveals in both cases reduced accumulation in the inner marginal zone. These observations suggest that chemokine receptor signaling and the integrins LFA-1 and {alpha}4ß1 function together to promote lymphocyte transit from the marginal zone into white pulp cords.

Key Words: splenic white pulp • LFA-1 • {alpha}4ß1 • lymphocyte homing • marginal zone


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