BACKGROUND The BTB domain of B-cell lymphoma 6 (BCL6) protein was identified as a therapeutic target for B-cell lymphoma. This study compared the pharmacokinetics (PK) of the BCL6 BTB inhibitor (FX1) between mice and macaques, as well as evaluating its lymphoid suppressive effect in uninfected macaques with lymphoid hyperplasia. MATERIALS AND METHODS Eight uninfected adult Indian rhesus macaques (Macaca mulatta) were used in the study, four animals carrying lymphoid tissue hyperplasia. Plasma FX1 levels were measured by HPLC-MS/MS. Lymph node biopsies were used for H&E and immunohistochemistry staining, as well as mononuclear cell isolation for flow cytometry analysis. RESULTS Inhibition of the BCL6 BTB domain with FX1 led to a reduction in the frequency of GC, Tfh CD4+ , and Tfh precursor cells, as well as resolving lymphoid hyperplasia, in rhesus macaques. CONCLUSIONS B-cell lymphoma 6 inhibition may represent a novel strategy to reduce hyperplastic lymphoid B-cell follicles and decrease Tfh cells.

中文翻译：

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BCL6通过FX1处理对BTB的特异性抑制作用降低了印度恒河猴（Macaca mulatta）中的Tfh细胞并逆转了淋巴滤泡增生。

背景技术B细胞淋巴瘤6（BCL6）蛋白的BTB结构域被确定为B细胞淋巴瘤的治疗靶标。这项研究比较了BCL6 BTB抑制剂（FX1）在小鼠和猕猴之间的药代动力学（PK），并评估了其在未感染的具有淋巴样增生的猕猴中的淋巴抑制作用。材料与方法本研究使用了八只未感染的成年印度恒河猴（Macaca mulatta），四只动物患有淋巴组织增生。通过HPLC-MS / MS测量血浆FX1水平。淋巴结活检用于H＆E和免疫组织化学染色，以及单核细胞分离用于流式细胞术分析。结果FX1抑制BCL6 BTB结构域导致GC，Tfh CD4 +和Tfh前体细胞的频率降低，并解决了淋巴样增生，在恒河猴中。结论抑制B细胞淋巴瘤6可能代表一种减少增生性淋巴B细胞滤泡和减少Tfh细胞的新策略。