Human T-follicular helper and T-follicular regulatory cell maintenance is independent of germinal centers
Human T-follicular helper and T-follicular regulatory cell maintenance is independent of germinal centers
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DOI：
10.1182/blood-2014-07-585976
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发表时间：
2014-10-23
期刊：
影响因子：
20.3
通讯作者：
Smith, Kenneth G. C.
中科院分区：
文献类型：
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作者：
Wallin, Elizabeth F.;Jolly, Elaine C.;Smith, Kenneth G. C.
抗CD20的单抗美罗华(RTX)在淋巴瘤和自身免疫性疾病的治疗中耗尽B细胞，并有助于跨越免疫屏障的移植中同种异体抗体的减少。RTX对T细胞的影响还没有得到很好的描述。T滤泡辅助细胞(TFH)向生发中心(GC)B细胞提供生长和分化信号以支持抗体的产生，抑制性T滤泡调节细胞(TFR)调节这一反应。在小鼠中，Tfh和Tfr完全依赖于B细胞的形成和GC的维持。在这项研究中，我们证明了RTX治疗导致人类淋巴结中缺乏GC B细胞，而不影响TFH或TFR细胞群。这些数据表明，人类转铁蛋白和转铁蛋白受体不需要持续的GC反应来维持它们。RTX治疗后持续的TFH和TFR可能允许一旦B细胞池开始恢复，病理性GC反应的快速重建。RTX治疗后维持缓解的策略将需要考虑FH的这种持久性。
The monoclonal anti-CD20 antibody rituximab (RTX) depletes B cells in the treatment of lymphoma and autoimmune disease, and contributes to alloantibody reduction in transplantation across immunologic barriers. The effects of RTX on T cells are less well described. T-follicular helper (Tfh) cells provide growth and differentiation signals to germinal center (GC) B cells to support antibody production, and suppressive T-follicular regulatory (Tfr) cells regulate this response. In mice, both Tfh and Tfr are absolutely dependent on B cells for their formation and on the GC for their maintenance. In this study, we demonstrate that RTX treatment results in a lack of GC B cells in human lymph nodes without affecting the Tfh or Tfr cell populations. These data demonstrate that human Tfh and Tfr do not require an ongoing GC response for their maintenance. The persistence of Tfh and Tfr following RTX treatment may permit rapid reconstitution of the pathological GC response once the B-cell pool begins to recover. Strategies for maintaining remission after RTX therapy will need to take this persistence of fh into account.