The peritoneal cavity provides a protective niche for B1 and conventional B lymphocytes during anti-CD20 immunotherapy in mice
The peritoneal cavity provides a protective niche for B1 and conventional B lymphocytes during anti-CD20 immunotherapy in mice
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DOI：
10.4049/jimmunol.174.7.4389
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发表时间：
2005-04-01
影响因子：
4.4
通讯作者：
Tedder, TF
中科院分区：
文献类型：
--
作者：
Hamaguchi, Y;Uchida, J;Tedder, TF
尽管抗CD 20免疫疗法有效地治疗人类淋巴瘤和自身免疫性疾病，但免疫疗法对组织B细胞及其亚群的体内作用通常是未知的。为了解决这个问题，在小鼠模型中使用抗小鼠CD 20 mAb，其中可以在体内评估组织B细胞耗竭的程度和动力学。CD 20 mAb处理在2天内耗尽了大多数成熟B细胞，到第7天骨髓、血液、脾脏、淋巴结和肠道相关淋巴组织中95-98%的B细胞耗尽，包括边缘区和滤泡B细胞。CD 20 mAb处理后剩余的少量脾B细胞包括前B细胞、未成熟细胞、过渡细胞和一些低水平表达CD 20的B1 B细胞。相比之下，腹膜腔B细胞表达正常的CD 20密度，并被CD 20 mAb包被，但到第7天只有30-43%的B1细胞和43-78%的B2细胞被耗尽。过继转移至腹腔的脾B细胞对mAb诱导的耗竭具有类似的抗性，而转移至脾的B细胞被耗竭。然而，腹膜B1和B2细胞被有效地耗尽单克隆抗体治疗的野生型和C3缺陷型小鼠巯基乙酸诱导的单核细胞迁移到这个否则特权的小生境。在用CD 20 mAb处理的FcR缺陷小鼠中，炎症诱导的效应细胞没有促进腹膜腔B细胞耗竭。因此，在抗CD 20免疫治疗过程中，淋巴组织和腹膜内的大多数CD 20（+）细胞和B细胞亚群可以通过C依赖性但不依赖于G的途径在体内有效地清除。
Although anti-CD20 immunotherapy effectively treats human lymphoma and autoimmune disease, the in vivo effect of immunotherapy on tissue B cells and their subsets is generally unknown. To address this, anti-mouse CD20 mAbs were used in a mouse model in which the extent and kinetics of tissue B cell depletion could be assessed in vivo. CD20 mAb treatment depleted most mature B cells within 2 days, with 95-98% of B cells in the bone marrow, blood, spleen, lymph nodes, and gut-associated lymphoid tissues depleted by day 7, including marginal zone and follicular B cells. The few spleen B cells remaining after CD20 mAb treatment included pre-B, immature, transitional, and some B1 B cells that expressed CD20 at low levels. By contrast, peritoneal cavity B cells expressed normal CD20 densities and were coated with CD20 mAb, but only 30-43% of B1 cells and 43-78% of B2 cells were depleted by day 7. Spleen B cells adoptively transferred into the peritoneal cavity were similarly resistant to mAb-induced depletion, while transferred B cells that had migrated to the spleen were depleted. However, peritoneal B1 and B2 cells were effectively depleted in mAb-treated wild-type and C3-deficient mice by thioglycolate-induced monocyte migration into this otherwise privileged niche. Inflammation-elicited effector cells did not promote peritoneal cavity B cell depletion in FcR-deficient mice treated with CD20 mAb. Thus, the majority of CD20(+) cells and B cell subsets within lymphoid tissues and the peritoneum could be depleted efficiently in vivo through C-dependent, but Gindependent pathways during anti-CD20 immunotherapy.