The Journal of Experimental Medicine
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Published 3 October 2005. doi:10.1084/jem.20042433
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 7, 955-965
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ARTICLE

 TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis

Thomas T. Chen1,2, Li Li1, Dong-Hui Chung2, Christopher D.C. Allen3, Suzy V. Torti6, Frank M. Torti6, Jason G. Cyster3,4, Chih-Ying Chen5, Frances M. Brodsky3,5, Eréne C. Niemi2, Mary C. Nakamura1,2, William E. Seaman1,2,3, and Michael R. Daws1,2

1 Veterans Administration Medical Center, San Francisco, CA 94121
2 Department of Medicine, University of California San Francisco, CA 94143
3 Department of Microbiology and Immunology, University of California San Francisco, CA 94143
4 Howard Hughes Medical Institute, University of California San Francisco, CA 94143
5 The G.W. Hooper Foundation and the Departments of Biopharmaceutical Sciences and Pharmaceutical Chemistry, University of California San Francisco, CA 94143
6 Department of Cancer Biology, Wake Forest University Health Sciences, Wake Forest University, Winston-Salem, NC 27157

CORRESPONDENCE William E. Seaman: bseaman{at}medicine.ucsf.edu

T cell immunoglobulin-domain and mucin-domain (TIM) proteins constitute a receptor family that was identified first on kidney and liver cells; recently it was also shown to be expressed on T cells. TIM-1 and -3 receptors denote different subsets of T cells and have distinct regulatory effects on T cell function. Ferritin is a spherical protein complex that is formed by 24 subunits of H- and L-ferritin. Ferritin stores iron atoms intracellularly, but it also circulates. H-ferritin, but not L-ferritin, shows saturable binding to subsets of human T and B cells, and its expression is increased in response to inflammation. We demonstrate that mouse TIM-2 is expressed on all splenic B cells, with increased levels on germinal center B cells. TIM-2 also is expressed in the liver, especially in bile duct epithelial cells, and in renal tubule cells. We further demonstrate that TIM-2 is a receptor for H-ferritin, but not for L-ferritin, and expression of TIM-2 permits the cellular uptake of H-ferritin into endosomes. This is the first identification of a receptor for ferritin and reveals a new role for TIM-2.

Abbreviations used: GC, germinal center; IHC, immunohistochemistry; RT, room temperature; TIM, T cell immunoglobulin domain and mucin domain; TREM, triggering receptor expressed on myeloid cells.

T.T. Chen and L. Li contributed equally to this work.

M.R. Daws' present address is Department of Anatomy, University of Oslo, Oslo, Norway NO317.


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