title: Follicular lymphoma-protective HLA class II variants correlate with increased HLA-DQB1 protein expression.
abstract: Multiple follicular lymphoma (FL) susceptibility single-nucleotide polymorphisms in the human leukocyte antigen (HLA) class I and II regions have been identified, including rs6457327, rs3117222, rs2647012, rs10484561, rs9268853 and rs2621416. Here we validated previous expression quantitative trait loci results with real-time reverse transcription quantitative PCR and investigated protein expression in B-lymphoblastoid cell lines and primary dendritic cells using flow cytometry, cell-based enzyme-linked immunosorbent assay and western blotting. We confirmed that FL-protective rs2647012-linked variants, in high linkage disequilibrium with the extended haplotype DRB1*15:01-DQA1*01:02-DQB1*06:02, correlate with increased HLA-DQB1 expression. This association remained significant at the protein level and was reproducible across different cell types. We also found that differences in HLA-DQB1 expression were not related to changes in activation markers or class II, major histocompatibility complex, transactivator expression, suggesting the role of an alternative regulatory mechanism. However, functional analysis using RegulomeDB did not reveal any relevant regulatory candidates. Future studies should focus on the clinical relevance of increased HLA-DQB1 protein expression facilitating tumor cell removal through increased immune surveillance.
authors.affiliation: Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, USA.
authors.forename: F C M
authors.initials: FC
authors.lastname: Sillé
authors.affiliation: Department of Epidemiology, Comprehensive Cancer Center, University of Alabama, Birmingham, AL, USA.
authors.forename: L
authors.initials: L
authors.lastname: Conde
authors.affiliation: Department of Epidemiology, Comprehensive Cancer Center, University of Alabama, Birmingham, AL, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, USA.
authors.forename: N K
authors.initials: NK
authors.lastname: Akers
authors.affiliation: Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sanchez
authors.affiliation: Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Maltbaek
authors.affiliation: Department of Epidemiology, Comprehensive Cancer Center, University of Alabama, Birmingham, AL, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Riby
authors.affiliation: Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Smith
authors.affiliation: Department of Epidemiology, Comprehensive Cancer Center, University of Alabama, Birmingham, AL, USA.
authors.forename: C F
authors.initials: CF
authors.lastname: Skibola
mesh_terms: D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D059866:HLA-DQ beta-Chains / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes / Q000235:genetics / Q000276:immunology; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008070:Lipopolysaccharides; D008213:Lymphocyte Activation; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000276:immunology
chemical_list: D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D008070:Lipopolysaccharides