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Updated: Jul 17, 2026
Induction of Experimental Autoimmune Encephalomyelitis in Mice and Evaluation of the Disease-dependent Distribution of Immune Cells in Various Tissues
Published on: May 8, 2016
Patterns of expression, membrane localization, and effects of ectopic expression suggest a function for MS4a4B, a
Hui Xu1, Mark S Williams, Lisa M Spain
1Department 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.
Abstract:
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.
Insights
The study reveals that MS4a4B protein expression is regulated during T-cell development. MS4a4B promotes T helper 1 (Th1) cell function and differentiation, impacting immune responses.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- The Membrane-spanning 4A (MS4A) gene family is linked to allergies and asthma.
- MS4a4B was previously reported in T helper 1 (Th1) but not T helper 2 (Th2) cells.
Purpose of the Study:
- To investigate the role and regulation of MS4a4B during T-cell development and function.
- To determine the impact of MS4a4B on T helper cell differentiation and cytokine production.
Main Methods:
- Gene expression screening during thymocyte development.
- Analysis of MS4a4B expression in various T cell subsets and natural killer (NK) cells.
- Cell surface localization and lipid raft association studies.
- T-cell receptor (TCR)-induced cytokine production assays following MS4a4B overexpression.
Main Results:
- MS4a4B expression is dynamically regulated during thymocyte development, appearing in immature and mature stages.
- MS4a4B is expressed on naive CD4+, CD8+ T cells, and NK cells, but not B cells.
- MS4a4B localizes to the cell surface and associates with lipid rafts, particularly upon T-cell activation.
- Overexpression of MS4a4B enhances TCR-induced Th1 cytokine production in CD4+ T cells.
Conclusions:
- MS4a4B expression is tightly controlled throughout T-cell development.
- MS4a4B plays a role in promoting Th1 cell function and/or differentiation.
- MS4a4B may be a key regulator in immune responses involving Th1 cells.
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