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
2,6-sialyltransferase mRNA forms
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
ST6Gal I (ß-galactoside
2,6-sialyltransferase, ST6N) elaborates the ubiquitously expressed
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,
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 812 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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