DISREGULATION OF LEUKOSIALIN (CD43, LY48, SIALOPHORIN) EXPRESSION IN THE B-CELL LINEAGE OF TRANSGENIC MICE INCREASES SPLENIC B-CELL NUMBER AND SURVIVAL

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.