Octamer binding protein 2 (Oct2) regulates PD-L2 gene expression in B-1 cells through lineage-specific activity of a unique, intronic promoter.
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.
Kaku
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Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, North Shore LIJ Health System, Manhasset, NY 11030, USA.
Rothstein
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D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D050811:Octamer Transcription Factor-1 / Q000235:genetics / Q000378:metabolism; D050813:Octamer Transcription Factor-2 / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity / Q000502:physiology; D010455:Peptides / Q000378:metabolism*; D061027:Programmed Cell Death 1 Ligand 2 Protein; D011401:Promoter Regions, Genetic / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology
D050811:Octamer Transcription Factor-1; D050813:Octamer Transcription Factor-2; C556978:Pdcd1lg2 protein, mouse; D010455:Peptides; C494166:Pou2f1 protein, mouse; C489206:Pou2f2 protein, mouse; D061027:Programmed Cell Death 1 Ligand 2 Protein