Disregulation of Leukosialin (CD43, Ly48, Sialophorin) Expression in the B- Cell Lineage of Transgenic Mice Increases Splenic B-Cell Number and Survival

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 92; no. 2; pp. 626 - 630
• Main Authors: Dragone, Leonard L., Barth, Richard K., Sitar, Kristie L., Disbrow, Gary L., Frelinger, John G.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 17.01.1995; National Acad Sciences; National Academy of Sciences
• Subjects: Animals; Antigens, CD; Apoptosis; B lymphocytes; B-Lymphocytes - immunology; Cell Count; Cell Differentiation; Cell lines; Cell Survival; Cellular biology; Cytometry; Enhancer Elements, Genetic - genetics; Flow Cytometry; Gene Expression Regulation; Hematopoietic Stem Cells - immunology; Immunity (Disease); Leukosialin; Mice; Mice, Transgenic; Molecules; Plasma cells; Proteins; Recombinant Fusion Proteins - biosynthesis; Rodents; Sialoglycoproteins - biosynthesis; Spleen; Spleen - cytology; Spleen - immunology; Spleen cells; T lymphocytes; Transgenes
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.2.626

Leukosialin (also known as Ly48, CD43, and sialophorin) is a major cell surface sialoglycoprotein found on a variety of hematopoietically derived cells. The precise function of this molecule is poorly understood but it has been implicated in cell proliferation and intercellular adhesion. We developed a transgenic mouse model to assess leukosialin's function in vivo. Our approach was to alter mouse CD43 (mCD43) expression in the B-cell lineage where it is tightly regulated, by expressing it in peripheral B cells where it is normally absent. To drive expression of leukosialin in mature B cells, the immunoglobulin heavy chain enhancer was fused to the mCD43 gene. mCD43-immunoglobulin heavy chain enhancer transgenic mice display splenomegaly due to increased numbers of B cells. Transgenic B cells show a striking increase in their ability to survive in vitro compared to B cells from nontransgenic control mice. This prolonged survival is reflected in a decreased susceptibility to apoptosis. These observations suggest that mCD43 plays an important role in the regulation of B-cell survival. The alteration of the temporal expression, or "disregulation," of a gene in transgenic mice provides a general strategy for elucidating the in vivo role of other molecules involved in cell signaling and adhesion.