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Developmental Immunology
Volume 7 (2000), Issue 2-4, Pages 209-225
http://dx.doi.org/10.1155/2000/94616

Balancing Thymocyte Adhesion and Motility: A Functional Linkage Between β1 Lntegrins and The Motility Receptor RHAMM

1Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, AB, Canada
2Department of Oncology, Cross Cancer Institute, 11560 University Ave. Edmonton, AB, T6G 1Z2, Canada

Copyright © 2000 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Thymocyte differentiation involves several processes that occur in different anatomic sites within the thymus. Therefore, thymocytes must have the ability to respond to signals received from stromal cells and adopt either adhesive or motile behavior. We will discuss our data indicating human thymocytes use α4β1 integrin, α5β1 integrin and RHAMM to mediate these activities. Immature multinegative (MN; CD3–4–8–19-) thymocytes use α4β1 and α5β1 integrins to mediate weak and strong adhesion. This subset also uses α4β1 integrin to mediate motility. As thymocytes differentiate, they begin to express and use RHAMM to mediate motility in conjunction with α4β1 and α5β1 integrins. Motile thymocytes use β1 integrins to maintain weakly adhesive contacts with substrate to provide traction for locomoting cells, thus weak adhesion is a requirement of motile behavior. Hyaluronan (HA) is also required by thymocytes to mediate motility. HA binding to cell surface RHAMM redistributes intracellular RHAMM to the cell surface where it functions to mediate motility. We propose that the decision to maintain adhesive or motile behavior is based on the balance between low and high avidity binding conformations of β1 integrins on thymocytes and that RHAMM:HA interactions decrease high avidity binding conformations of integrins pushing the balance toward motile behavior.