Department of Immunology and Pathology, Alfred Medical Research and Education Precinct, Monash University, Melbourne, VIC, Australia.
Australian Centre for Blood Diseases, Central Clinical School, Monash University, Melbourne, VIC, Australia.
Immunol Cell Biol. 2022 Oct;100(9):705-717. doi: 10.1111/imcb.12578. Epub 2022 Aug 17.
Aberrant expression of the proto-oncogene BCL6 is a driver of tumorigenesis in diffuse large B cell lymphoma (DLBCL). Mice overexpressing BCL6 from the B cell-specific immunoglobulin heavy chain μ intron promoter (Iμ-Bcl6 ) develop B cell lymphomas with features typical of human DLBCL. While the development of B cell lymphoma in these mice is tightly controlled by T cells, the mechanisms of this immune surveillance are poorly understood. Here we show that CD4 T cells contribute to the control of lymphoproliferative disease in lymphoma-prone Iμ-Bcl6 mice. We reveal that this CD4 T cell immuno-surveillance requires signaling by the co-stimulatory molecule CD137 ligand (CD137L; also known as 4-1BBL), which may promote the transition of pre-malignant B cells with an activated phenotype into the germinal center stage via reverse signaling, preventing their hazardous accumulation. Thus, CD137L-mediated CD4 T cell immuno-surveillance adds another layer of protection against B cell malignancy to that provided by CD8 T cell cytotoxicity.
原癌基因 BCL6 的异常表达是弥漫性大 B 细胞淋巴瘤（DLBCL）肿瘤发生的驱动因素。在 B 细胞特异性免疫球蛋白重链 μ 内含子启动子（Iμ-Bcl6）的过度表达的小鼠中，会发展出具有典型人类 DLBCL 特征的 B 细胞淋巴瘤。虽然这些小鼠中的 B 细胞淋巴瘤的发展受到 T 细胞的严格控制，但这种免疫监视的机制尚不清楚。在这里，我们表明 CD4 T 细胞有助于控制易发生淋巴瘤的 Iμ-Bcl6 小鼠中的淋巴增殖性疾病。我们揭示了这种 CD4 T 细胞免疫监视需要共刺激分子 CD137 配体（CD137L；也称为 4-1BBL）的信号转导，该信号转导可能通过反向信号促进具有激活表型的恶性前 B 细胞过渡到生发中心阶段，从而防止它们危险地积累。因此，CD137L 介导的 CD4 T 细胞免疫监视为 CD8 T 细胞细胞毒性提供了针对 B 细胞恶性肿瘤的另一层保护。
