Follicular lymphoma-protective HLA class II variants correlate with increased HLA-DQB1 protein expression

Fenna Sille, L. Conde, J. Zhang, N. K. Akers, S. Sanchez, J. Maltbaek, J. E. Riby, M. T. Smith, C. F. Skibola

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)133-136
Number of pages4
JournalGenes and Immunity
Volume15
Issue number2
DOIs
Publication statusPublished - 2014
Externally publishedYes

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Keywords

  • Follicular lymphoma
  • Gene expression
  • Human leukocyte antigen
  • Protein expression

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

Sille, F., Conde, L., Zhang, J., Akers, N. K., Sanchez, S., Maltbaek, J., ... Skibola, C. F. (2014). Follicular lymphoma-protective HLA class II variants correlate with increased HLA-DQB1 protein expression. Genes and Immunity, 15(2), 133-136. https://doi.org/10.1038/gene.2013.64