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Glycobiology, 2000, Vol. 10, No. 1 67-75
© 2000 Oxford University Press

Murine B cell differentiation is accompanied by programmed expression of multiple novel ß-galactoside {alpha}2,6-sialyltransferase mRNA forms

Sherry A. Wuensch, Ruea Yea Huang, Jonathan Ewing1, XueLian Liang2 and Joseph T. Y. Lau3

Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA

ST6Gal I (ß-galactoside {alpha}2,6-sialyltransferase, ST6N) elaborates the ubiquitously expressed {alpha}2,6-sialyl linkage. A number of ST6Gal I mRNA isoforms, differing only in their 5'-UT regions, is transcribed from a single mouse gene, Siat1. In B-lineage cells, {alpha}2,6-sialic acid serves as extracellular ligand for CD22, a participant in cell activation via an intracellular signaling network of tyrosine kinases and SHP phosphastase. Activation and terminal differentiation of mature B cells into plasma cells is accompanied by the appearance of at least four distinct ST6Gal I mRNA isoforms. Resting splenic B-lymphocytes isolated from 8–12 wk C56Bl/6 mice expressed almost exclusively the Exons Q+O-containing form, which is the likely homolog to the previously documented human Y+Z and rat –1+0 forms. In vitro activation using recombinant CD40-ligand and conditioned media from T-helper cells resulted in a 2- to 3-fold elevation of overall ST6Gal I mRNA abundance by Day 3. This coincided with repression of the Q+O form, and appearance of three new isoforms containing 5'-untranslated sequences X1, X2, or X3. The X1 form persisted through Day 10, when the transition of B cells to plasma cells was completed as evidence by disappearance of CD22 mRNA. In contrast, the X2 form only transiently appeared at Day 3 and declined to barely detectable levels by Day 7. Expression of the X3 form, a minor mRNA form, paralleled the X2 form. The divergent 5'-UT exons are dispersed over 69 kb of linear genomic space of Siat1. Mutually exclusive utilization of these 5'-UT exons in transcripts predicts separate and distinct promoter regulatory regions for each mRNA isoform.

1 Present address: Millennium Pharmaceuticals, Inc., 640 Memorial Drive, Cambridge, MA 02139

2 Present address: Piscataway, NJ

3 To whom correspondence should be addressed


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