Regulatory B cells preferentially accumulate in tumor-draining lymph nodes and promote tumor growth.
Regulatory B cells preferentially accumulate in tumor-draining lymph nodes and promote tumor growth.
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DOI：
10.1038/srep12255
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发表时间：
2015-07-20
影响因子：
4.6
通讯作者：
Ruddell A
中科院分区：
文献类型：
--
作者：
Ganti SN;Albershardt TC;Iritani BM;Ruddell A
我们之前的研究发现，免疫活性小鼠后足垫中 B16-F10 黑色素瘤的生长会诱导肿瘤引流腘淋巴结 (TDLN) 内明显的 B 细胞积聚。这种 B 细胞积累会驱动 TDLN 重塑，进而促进转移，表明 TDLN B 细胞具有促肿瘤作用。在这里，我们展示了携带 B16-F10 黑色素瘤的小鼠中淋巴细胞的表型特征，确定了 TDLN 中 T2-MZP B 细胞的优先积累。将荷瘤小鼠的非引流淋巴结和脾脏与初始小鼠的淋巴结和脾脏进行比较，确定这种 B 细胞积累模式仅限于 TDLN。用 T2-MZP B 细胞而非其他 B 细胞亚群重建的 B 细胞缺陷且具有免疫功能的小鼠显示出肿瘤生长加速，这表明 T2-MZP B 细胞在荷瘤小鼠中具有调节活性。然而，与脾调节性 B 细胞不同，这些 TDLN B 细胞没有表现出 IL-10 产量增加，也没有促进 TDLN 中 Treg 的生成。这些发现表明，肿瘤最初通过淋巴引流发出信号，刺激 T2-MZP 调节性 B 细胞的优先积累。这种局部反应可能是产生免疫抑制环境以允许肿瘤生长和转移的早期且关键的步骤。
Our previous studies found that B16-F10 melanoma growth in the rear footpad of immunocompetent mice induces marked B cell accumulation within tumor-draining popliteal lymph nodes (TDLN). This B cell accumulation drives TDLN remodeling that precedes and promotes metastasis, indicating a tumor-promoting role for TDLN B cells. Here we show that phenotypic characterization of lymphocytes in mice bearing B16-F10 melanomas identifies preferential accumulation of T2-MZP B cells in the TDLN. Comparison of non-draining LNs and spleens of tumor-bearing mice with LNs and spleens from naïve mice determined that this pattern of B cell accumulation was restricted to the TDLN. B cell-deficient and immunocompetent mice reconstituted with T2-MZP B cells but not with other B cell subsets displayed accelerated tumor growth, demonstrating that T2-MZP B cells possess regulatory activity in tumor-bearing mice. Unlike splenic regulatory B cells, however, these TDLN B cells did not exhibit increased IL-10 production, nor did they promote Treg generation in the TDLN. These findings demonstrate that tumors initially signal via the lymphatic drainage to stimulate the preferential accumulation of T2-MZP regulatory B cells. This local response may be an early and critical step in generating an immunosuppressive environment to permit tumor growth and metastasis.