Octamer binding protein 2 (Oct2) regulates PD-L2 gene expression in B-1 cells through lineage-specific activity of a unique, intronic promoter

PD-L2 expression extends beyond macrophages/dendritic cells to B-1 B cells, a distinct B cell lineage that is responsible for natural immunoglobulin and which is repertoire skewed toward autoreactive specificities. PD-L2 expression is constitutive in B-1 cells, whereas it is inducible in other cell types, suggesting that PD-L2 is regulated differently in the former versus the latter, and this proved to be the case, both in transcription and promotion. B-1 cells express a PD-L2 transcript that lacks exon1, in contrast to macrophages/dendritic cells for which exon1 is included, reflecting a unique start site upstream of exon2. PD-L2 transcription in B-1 cells is regulated by a novel intronic promoter located between exon1 and exon2. This intronic promoter binds Oct1 and Oct2, and although these transcription factors are present in all B cells, Oct2 binding is found in vivo only in B-1 cells and not PD-L2 negative B-2 cells. Moreover, the proximal promoter upstream of exon1 that is active in macrophages is inactive in B-1 cells. Thus, PD-L2 expression is regulated by two different promoters that function in a lineage-specific fashion, with the B-1-specific promoter being constitutively active as a result of Oct1 and Oct2 binding.