EPHRIN-B1 is critical in T-cell development and thymocyte TCR signaling strength

doi:10.1074/jbc.M510320200

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Papers In Press, published online ahead of print February 13, 2006
J. Biol. Chem, 10.1074/jbc.M510320200
Submitted on September 20, 2005
Revised on February 7, 2006
Accepted on February 13, 2006

EPHRIN-B1 is critical in T-cell development and thymocyte TCR signaling strength

Guang Yu, Jianning Mao, Yulian Wu, Hongyu Luo, and Jiangping Wu

Medicine Dept., University of Montreal, Notre-Dame Hospital, Montreal, Qc H2L 4M1

Corresponding Author: jianping.wu{at}umontreal.ca

Eph kinases are the largest family of receptor tyrosine kinases, and their ligands, ephrins (EFN), are also cell surface molecules. In this study, we investigated the role of EFNB1 and the Ephs it interacts with (collectively called EFNB1 receptors) in mouse T-cell development. In the thymus, CD8 single positive (SP) and CD4CD8 double positive (DP) cells expressed high levels of EFNB1 and EFNB1 receoptors, while CD4 SP cells had moderate expression of both. Soluble EFNB1-Fc in fetal thymus organ culture (FTOC) caused significant subpopulation ratio skew, with increased CD4 SP and CD8 SP, and decreased DP percentage, while the cellularity of the thymus remained constant. Moreover, in EFNB1-treated FTOC, CD117+, CD25+, DP, CD4 SP and CD8 SP cells all had significantly enhanced proliferation history, according to BrdU uptake. In vitro culture of isolated thymocytes revealed that EFNB1-Fc on solid phase protected thymocytes from anti-CD3-induced apoptosis, with concomitant augmentation of several anti-apoptotic factors, particularly in CD4 SP and CD8 SP cells; on the other hand, soluble EFNB1-Fc promoted anti-CD3-induced apoptosis, as was the case in vivo. This study reveals that EFNB1 and EFNB1 receptors are critical in thymocyte development.

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