Background: B cells can function as antigen-presenting cells by presenting antigens captured by the B-cell receptor (BCR) on Class II Major Histocompatibility Complex (MHC II) to T cells. In addition, B-cells can also maintain immune homeostasis by expressing PD-L1 and suppressing T-cell activity. Epstein-Barr virus (EBV) infection can disrupt B-cell function and lead to B cell malignancies, including diffuse large B-cell lymphoma (DLBCL). Here we show that EBV-positive DLBCL (EBV+ DLBCL) has decreased expression of BCR and MHC II, but over-expressed PD-L1, which may lead to immune evasion. Methods: An EBV+ DLBCL cohort (n = 30) and an EBV- DLBCL control cohort (n = 83) were established. Immunostaining of PD-L1, MHC II, MHC II Transactivator (CIITA) and pBTK was performed on automated stainer. H-score was used to denote the results of staining of PD-L1 and pBTK. Break apart and deletion of CIITA locus was studied by fluorescent in situ hybridization. Surface immunoglobulin mean fluorescent insensitivity (MFI) was detected by flow cytometry to demonstrate the level BCR. Results: EBV+ DLBCL showed significantly lower expression of CIITA and MHC II compared to EBV- DLBCL. Genetic aberrations involving CIITA were also more common in EBV+ DLBCL, with 23% break apart events and 6% deletion events, comparted to 2% break apart and 0% deletion in EBV- DLBCL. In addition to the loss of antigen presentation molecule, the antigen capture receptor, BCR, was also down-regulated in EBV+ DLBCL. Accordingly, BCR signaling was also significantly decreased in EBV+ DLBCL as denoted by the respective pBTK levels. Conclusions: EBV+ DLBCL shows over expression of the T-cell inhibitory ligand, PD-L1. Antigen capture and presentation system were disrupted, and T-cell inhibitory molecule was hijacked in EBV+ DLBCL, which may contribute to immune escape in this high risk disease. Therapies targeting these aberrations may improve the outcome of patients with EBV+ DLBCL.

中文翻译：

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爱泼斯坦-巴尔病毒阳性的弥漫性大B细胞淋巴瘤具有破坏抗原捕获/呈递和劫持性T细胞抑制的特征。

背景：B细胞可以通过将II类主要组织相容性复合物（MHC II）上的B细胞受体（BCR）捕获的抗原呈递给T细胞来充当抗原呈递细胞。此外，B细胞还可以通过表达PD-L1和抑制T细胞活性来维持免疫稳态。爱泼斯坦巴尔病毒（EBV）感染会破坏B细胞功能并导致B细胞恶性肿瘤，包括弥漫性大B细胞淋巴瘤（DLBCL）。在这里，我们显示EBV阳性DLBCL（EBV + DLBCL）降低了BCR和MHC II的表达，但是过表达的PD-L1可能导致免疫逃逸。方法：建立EBV + DLBCL对照队列（n = 30）和EBV- DLBCL对照队列（n = 83）。PD-L1，MHC II，MHC II反式激活剂（CIITA）和pBTK的免疫染色在自动染色机上进行。H分数用于表示PD-L1和pBTK的染色结果。通过荧光原位杂交研究了CIITA基因座的断裂和缺失。通过流式细胞仪检测表面免疫球蛋白的平均荧光不敏感性（MFI），以证明BCR的水平。结果：与EBV-DLBCL相比，EBV + DLBCL显示CIITA和MHC II的表达明显降低。涉及CIITA的遗传畸变在EBV + DLBCL中也更为常见，具有23％的断裂事件和6％的缺失事件，相当于EBV- DLBCL的2％断裂和0％缺失。除了丢失抗原呈递分子外，EBV + DLBCL中的抗原捕获受体BCR也被下调。因此，如相应的pBTK水平所示，EBV + DLBCL中的BCR信号也显着降低。结论：EBV + DLBCL显示T细胞抑制性配体PD-L1过表达。抗原捕获和呈递系统被破坏，T细胞抑制分子被劫持在EBV + DLBCL中，这可能有助于这种高危疾病的免疫逃逸。针对这些畸变的疗法可能会改善EBV + DLBCL患者的预后。