Dynamic changes of the normal B lymphocyte repertoire in CLL in response to ibrutinib or FCR chemo-immunotherapy
Dynamic changes of the normal B lymphocyte repertoire in CLL in response to ibrutinib or FCR chemo-immunotherapy
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DOI：
10.1080/2162402x.2017.1417720
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发表时间：
2018-01-01
期刊：
影响因子：
7.2
通讯作者：
Binder, Mascha
中科院分区：
文献类型：
--
作者：
Schliffke, Simon;Sivina, Mariela;Binder, Mascha
使用下一代免疫球蛋白（IGH）测序和流式细胞术，我们的特点的组成，多样性和非恶性B细胞的动态与布鲁顿酪氨酸激酶（BTK）抑制剂伊布替尼治疗或化学免疫治疗与氟达拉滨，环磷酰胺，利妥昔单抗（FCR）的患者。在伊曲替尼治疗期间，非恶性B细胞数量下降，但患者保持稳定的IGH多样性和恒定的IGH突变B细胞分数。这表明在伊鲁替尼治疗期间部分保存了抗原经历的B细胞，但用初始B细胞对正常B细胞池的补充受损。相反，在FCR后，我们注意到正常B细胞的恢复，具有未突变IGH的B细胞显著占优势。这种模式与预先存在的抗原经历的B细胞的缺失，随后用抗原初始B细胞进行库更新是相容的。B细胞动力学中这些相反的模式可能导致对新抗原与回忆抗原的不同反应，这需要进一步定义。
Using next-generation immunoglobulin (IGH) sequencing and flow cytometry, we characterized the composition, diversity and dynamics of non-malignant B cells in patients undergoing treatment with the Bruton tyrosine kinase (BTK) inhibitor ibrutinib or chemo-immunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR). During ibrutinib therapy, non-malignant B cell numbers declined, but patients maintained stable IGH diversity and constant fractions of IGH-mutated B cells. This indicates partial preservation of antigen-experienced B cells during ibrutinib therapy, but impaired replenishment of the normal B cell pool with naive B cells. In contrast, after FCR we noted a recovery of normal B cells with a marked predominance of B cells with unmutated IGH. This pattern is compatible with a deletion of pre-existing antigen-experienced B cells followed by repertoire renewal with antigen-naive B cells. These opposite patterns in B cell dynamics may result in different responses towards neoantigens versus recall antigens, which need to be further defined.