PMID- 24304973 OWN - NLM STAT- MEDLINE DCOM- 20141118 LR - 20211021 IS - 1476-5470 (Electronic) IS - 1466-4879 (Print) IS - 1466-4879 (Linking) VI - 15 IP - 2 DP - 2014 Mar TI - Follicular lymphoma-protective HLA class II variants correlate with increased HLA-DQB1 protein expression. PG - 133-6 LID - 10.1038/gene.2013.64 [doi] AB - 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. FAU - Sille, F C M AU - Sille FC AD - Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, USA. FAU - Conde, L AU - Conde L AD - Department of Epidemiology, Comprehensive Cancer Center, University of Alabama, Birmingham, AL, USA. FAU - Zhang, J AU - Zhang J AD - Department of Epidemiology, Comprehensive Cancer Center, University of Alabama, Birmingham, AL, USA. FAU - Akers, N K AU - Akers NK AD - Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, USA. FAU - Sanchez, S AU - Sanchez S AD - Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, USA. FAU - Maltbaek, J AU - Maltbaek J AD - Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, USA. FAU - Riby, J E AU - Riby JE AD - Department of Epidemiology, Comprehensive Cancer Center, University of Alabama, Birmingham, AL, USA. FAU - Smith, M T AU - Smith MT AD - Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, USA. FAU - Skibola, C F AU - Skibola CF AD - Department of Epidemiology, Comprehensive Cancer Center, University of Alabama, Birmingham, AL, USA. LA - eng GR - R01 CA104682/CA/NCI NIH HHS/United States GR - R01 CA154643/CA/NCI NIH HHS/United States GR - CA104682/CA/NCI NIH HHS/United States GR - CA154643/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20131205 PL - England TA - Genes Immun JT - Genes and immunity JID - 100953417 RN - 0 (HLA-DQ beta-Chains) RN - 0 (HLA-DQB1 antigen) RN - 0 (Lipopolysaccharides) SB - IM MH - Cells, Cultured MH - Dendritic Cells/immunology MH - Gene Frequency MH - Genetic Predisposition to Disease MH - HLA-DQ beta-Chains/*biosynthesis/*genetics/immunology MH - Haplotypes/genetics/immunology MH - Humans MH - Linkage Disequilibrium/genetics MH - Lipopolysaccharides MH - Lymphocyte Activation MH - Lymphoma, Follicular/*genetics/immunology MH - Polymorphism, Single Nucleotide MH - Quantitative Trait Loci/immunology PMC - PMC6279234 MID - NIHMS547241 COIS- CONFLICT OF INTEREST The authors declare no conflict of interest. EDAT- 2013/12/07 06:00 MHDA- 2014/11/19 06:00 PMCR- 2018/12/04 CRDT- 2013/12/06 06:00 PHST- 2013/08/28 00:00 [received] PHST- 2013/10/30 00:00 [revised] PHST- 2013/10/30 00:00 [accepted] PHST- 2013/12/06 06:00 [entrez] PHST- 2013/12/07 06:00 [pubmed] PHST- 2014/11/19 06:00 [medline] PHST- 2018/12/04 00:00 [pmc-release] AID - gene201364 [pii] AID - 10.1038/gene.2013.64 [doi] PST - ppublish SO - Genes Immun. 2014 Mar;15(2):133-6. doi: 10.1038/gene.2013.64. Epub 2013 Dec 5.