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Blood, 15 March 2006, Vol. 107, No. 6, pp. 2400-2408.
Prepublished online as a Blood First Edition Paper on November 17, 2005; DOI 10.1182/blood-2005-08-3340.
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Submitted August 17, 2005
Accepted October 28, 2005
Patterns of expression, membrane localization, and effects of ectopic expression suggest a function for MS4a4B, a CD20 homologue in Th1 T cells
Hui Xu, Mark S Williams*, and Lisa M Spain
Department of Microbiology and Immunology and Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, USA
* Corresponding author; email: marwilliams{at}som.umaryland.edu.
The membrane-spanning 4A, (MS4A) family of proteins includes CD20, Fc RI and HTm4, whose genes are grouped in a chromosomal location that is associated with increased susceptibility to allergy and atopic asthma. One family member, Chandra/MS4a4B, was reported to be expressed in Th1 T cells, but not Th2 T cells. In the present study, MS4a4B was isolated in a screen of genes differentially expressed during thymocyte development. MS4a4B was detected in immature CD4-8-CD44+CD25- thymocytes, turned off during further stages of thymocyte development, and re-expressed in mature single-positive thymocytes. MS4a4B expression was found in naive CD8+ and CD4+ peripheral T cells and NK cells, but not in B cells. MS4a4B is expressed at the cell surface with its C-terminus located in the cytoplasm. When expressed in a T cell hybridoma by retroviral vector, MS4a4B protein constitutively associates with lipid raft microdomains while in primary T cells, endogenous MS4a4B protein becomes enriched in rafts after T cell activation. Overexpression of MS4a4B in primary CD4+ T cell blasts enhanced TCR-induced Th1 cytokine production. These results suggest that MS4a4B expression is tightly regulated during T cell development and that MS4a4B expression promotes Th1 function and/or differentiation.

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