Alternative splicing generates a short BCL6 (BCL6S) isoform encoding a compact repressor

BCL6 gene transcribes two main mRNA isoforms, variant 1 and variant 2, which have distinct transcription start sites. However, these two isoforms encode identical BCL6 protein. Recently, a third variant was sequenced from a human hippocampus cDNA library (DB465062). In this study, we cloned and sequenced a novel BCL6 spliced isoform (BCL6S) which lacks exon 7 that encodes the first two zinc fingers of BCL6. We found a splicing isoform, BCL6S, that excludes exon 7 but retains the last four of the six zinc fingers (ZFs) coding region of the BCL6 gene. BCL6S mRNA and protein were expressed in human cell lines and tissues that expressed BCL6, but accounted for a minor portion of BCL6 transcripts or protein. BCL6S protein was also detectable in BCL6 positive cells. BCL6S could form homodimers or heterodimers with BCL6 and could bind to classical BCL6-binding sites. Luciferase reporter assays demonstrated that BCL6S could effectively repress typical BCL6 target genes. BCL6S is a compact repressor that may have a functional role in normal and neoplastic germinal center B cells.