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Mutation analysis of the EBV ‐lymphoblastoid cell line cautions their use as antigen‐presenting cells
Author(s) -
Tan Qin,
Ku Wenjing,
Zhang Chaoting,
Heyilimu Palashati,
Tian Yuan,
Ke Yang,
Lu Zheming
Publication year - 2018
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/imcb.1030
Subject(s) - biology , nonsynonymous substitution , somatic hypermutation , mutation , immunogenicity , antigen , cytidine deaminase , genetics , gene , microbiology and biotechnology , antigen presenting cell , t cell , b cell , antibody , immune system , genome
Lymphoblastoid cell lines ( LCL s) have been widely used as professional antigen‐presenting cells ( APC s). However, neoantigen‐loaded LCL s could induce nonspecific T‐cell response, which could be due to expression of both Epstein–Barr virus ( EBV ) antigens and nonsynonymous mutations arising in LCL s. Since the number of passages could influence mutational characteristics of LCL s, and moreover extensive proliferation of LCL s in vitro is necessary to activate T cells for immunotherapy, we comprehensively profiled mutational characteristics by comparing eight sets of B cells and matched high‐passage LCL s using whole‐exome sequencing in order to assess the effect of nonsynonymous mutations arising in LCL s on nonspecific T‐cell response. We found 315 nongermline mutations (approximately 40mut/subject) randomly distributed across all chromosomes including 18 mutations in immunoglobulin V and J genes in eight LCL s, of which 137 candidate neoantigens (approximately 17mut/subject) were identified. The underlying mutational processes linked to EBV ‐transformed LCL s could be attributed to activation induced cytidine deaminase gene expression which contributes to cytosine mutation clusters in LCL s through cytosine deamination. Pathways significantly enriched by nonsilent mutations of each LCL were totally different among all LCL s. In conclusion, high‐passage LCL s may not be suitable to serve as APC s due to random nonsilent mutations, particularly for presentation of neoantigens of low immunogenicity, although further experimental proofs are needed.