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

ST6Gal I (beta-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 C56B1/6 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, lit 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 X-1, X-2, or X-3. The X-1 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 X-2 form only transiently appeared at Day 3 and declined to barely detectable levels by Day 7, Expression of the X-3 form, a minor mRNA form, paralleled the X-2 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.