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

Genes & Immunity volume 11, pages 55–66 (2010)Cite this article

Abstract

Programmed death-1 ligand 2 (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 exon 1, in contrast to macrophages/dendritic cells for which exon1 is included, reflecting a unique start site upstream of exon 2. PD-L2 transcription in B-1 cells is regulated by a novel intronic promoter located between exons 1 and 2. This intronic promoter binds Octamer binding protein 1 (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 exon 1 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 manner, with the B-1-specific promoter being constitutively active as a result of Oct1 and Oct2 binding.

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Acknowledgements

We are grateful to our colleagues for helpful discussions and technical assistance throughout the course of this study. This work was supported in part by USPHS grant AI029690, awarded by the National Institutes of Health.

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  1. Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, North Shore LIJ Health System, Manhasset, NY, USA

    H Kaku & T L Rothstein

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Correspondence to T L Rothstein.

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Kaku, H., Rothstein, T. Octamer binding protein 2 (Oct2) regulates PD-L2 gene expression in B-1 cells through lineage-specific activity of a unique, intronic promoter. Genes Immun 11, 55–66 (2010). https://doi.org/10.1038/gene.2009.68

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