Patterns of expression, membrane localization, and effects of ectopic expression suggest a function for MS4a4B, a CD20 homolog in Th1 T cells.
The membrane-spanning 4A (MS4A) family of proteins includes CD20, Fc epsilonRIbeta, 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 T helper 1 (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- CD8- CD44+ CD25- thymocytes, turned off during further stages of thymocyte development and reexpressed in mature single-positive thymocytes. MS4a4B expression was found in naive CD8+ and CD4+ peripheral T cells and natural killer (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 associated with lipid raft microdomains, whereas in primary T cells endogenous MS4a4B protein became enriched in rafts after T-cell activation. Overexpression of MS4a4B in primary CD4+ T-cell blasts enhanced T-cell receptor (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.
Xu
Hui
H
Department of Microbiology and Immunology, Center for Vascular and Inflammatory Diseases, The University of Maryland School of Medicine, 800 W Baltimore St, Baltimore, MD 21201, USA.
Williams
Mark S
MS
Spain
Lisa M
LM
D000818:Animals; D018951:Antigens, CD20; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology*; D007694:Killer Cells, Natural / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D021962:Membrane Microdomains / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D013601:T-Lymphocytes / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism*; D013950:Thymus Gland / Q000378:metabolism; D014162:Transfection
D018951:Antigens, CD20; D008565:Membrane Proteins; C411486:Ms4a4b protein, mouse