B2M mutation paves the way for immune tolerance in pathogenesis of Epstein-Barr virus positive diffuse large B-cell lymphomas

He, Miaoxia; Liu, Bin; Tang, Gusheng; Jiao, Lijuan; Liu, Xuefei; Yin, Shuyi; Wang, Tao; Chen, Jie; Gao, Lei; Ni, Xiong; Wang, Libin; Xu, Lili; Yang, Jianmin

doi:10.7150/jca.75813

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International Journal of Biological Sciences

International Journal of Medical Sciences

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Journal of Genomics

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J Cancer 2022; 13(15):3615-3622. doi:10.7150/jca.75813 This issue Cite

Research Paper

B2M mutation paves the way for immune tolerance in pathogenesis of Epstein-Barr virus positive diffuse large B-cell lymphomas

Miaoxia He^1*✉, Bin Liu^2*, Gusheng Tang², Lijuan Jiao¹, Xuefei Liu¹, Shuyi Yin¹, Tao Wang², Jie Chen², Lei Gao², Xiong Ni², Libin Wang², Lili Xu², Jianmin Yang^2✉

1. Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, China 200433.
2. Departments of Hematology, Changhai Hospital, Second Military Medical University, Shanghai, China 200433.
* These two authors have equal contributions

Citation:

He M, Liu B, Tang G, Jiao L, Liu X, Yin S, Wang T, Chen J, Gao L, Ni X, Wang L, Xu L, Yang J. B2M mutation paves the way for immune tolerance in pathogenesis of Epstein-Barr virus positive diffuse large B-cell lymphomas. J Cancer 2022; 13(15):3615-3622. doi:10.7150/jca.75813. https://www.jcancer.org/v13p3615.htm

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Abstract

This study focused genetic pathogenesis and tumor microenvironment of Epstein-Barr virus (EBV) positive diffuse large B-cell lymphomas (DLBCL) in patients without immunodeficiency. DNA samples from these cases were sequenced by next generation sequencing (NGS) using a selected gene panel. Results revealed that most gene mutations were not specific for EBV positive DLBCL. However, B2M (β2-microglobulin) mutations were significantly increased and HLA-I or HLA-II expression was decreased in these cases, which was related to patient's poor outcome. B2M mutations and deregulation of B2M expression were further confirmed by Sanger sequencing and immunohistochemistry. Reducing the infiltration of CD8+ T lymphocytes, related to decreased expression of HLA-I or HLA-II was found in these patients. These results suggest that the mutations of B2M could cause the disruption of the expression and functions of this important subunit of HLA, leading to decreased expression of HLA-I or HLA-II and subsequently to reduce T lymphocyte infiltration in tumor tissues. The consequence of this event lessens the recognition and elimination of EBV+ tumor cells by host immunity and paves the way for the host immune tolerance to EBV+ tumor cells by evading immune recognition and escaping the T lymphocyte killing.

Keywords: Epstein-Barr virus, EBV+DLBCL, Gene mutation, B2M, Immune tolerance.

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APA

He, M., Liu, B., Tang, G., Jiao, L., Liu, X., Yin, S., Wang, T., Chen, J., Gao, L., Ni, X., Wang, L., Xu, L., Yang, J. (2022). B2M mutation paves the way for immune tolerance in pathogenesis of Epstein-Barr virus positive diffuse large B-cell lymphomas. Journal of Cancer, 13(15), 3615-3622. https://doi.org/10.7150/jca.75813.

ACS

He, M.; Liu, B.; Tang, G.; Jiao, L.; Liu, X.; Yin, S.; Wang, T.; Chen, J.; Gao, L.; Ni, X.; Wang, L.; Xu, L.; Yang, J. B2M mutation paves the way for immune tolerance in pathogenesis of Epstein-Barr virus positive diffuse large B-cell lymphomas. J. Cancer 2022, 13 (15), 3615-3622. DOI: 10.7150/jca.75813.

NLM

CSE

He M, Liu B, Tang G, Jiao L, Liu X, Yin S, Wang T, Chen J, Gao L, Ni X, Wang L, Xu L, Yang J. 2022. B2M mutation paves the way for immune tolerance in pathogenesis of Epstein-Barr virus positive diffuse large B-cell lymphomas. J Cancer. 13(15):3615-3622.

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