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BCL6 BTB‐specific inhibition via FX1 treatment reduces Tfh cells and reverses lymphoid follicle hyperplasia in Indian rhesus macaque ( Macaca mulatta )
Author(s) -
Cai Yanhui,
Watkins Meagan A.,
Xue Fengtian,
Ai Yong,
Cheng Huiming,
Midkiff Cecily C.,
Wang Xiaolei,
Alvarez Xavier,
Poli Adi Narayana Reddy,
Salvino Joseph M.,
Veazey Ronald S.,
Montaner Luis J.
Publication year - 2020
Publication title -
journal of medical primatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.31
H-Index - 42
eISSN - 1600-0684
pISSN - 0047-2565
DOI - 10.1111/jmp.12438
Subject(s) - bcl6 , lymphoma , lymphoid hyperplasia , flow cytometry , rhesus macaque , lymphatic system , hyperplasia , biology , macaque , follicular hyperplasia , germinal center , b cell , lymph node , immunohistochemistry , pathology , cancer research , immunology , antibody , medicine , endocrinology , paleontology
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.