A combination of IL-10 and direct contact with plasma cell tumors decreases CD23 expression on splenic B cells.
A combination of IL-10 and direct contact with plasma cell tumors decreases CD23 expression on splenic B cells.
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IL-10 的组合以及与浆细胞肿瘤的直接接触可降低脾 B 细胞上的 CD23 表达。
DOI：
10.4049/jimmunol.156.6.2124
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发表时间：
1996
影响因子：
4.4
通讯作者：
A. Mathur
中科院分区：
文献类型：
--
作者：
M. Ruzek;D. Billadeau;A. Mathur
我们和其他人先前已经发现，来自浆细胞荷瘤小鼠的脾B细胞表现出CD 23表达降低。在本研究中，我们进一步研究了浆细胞肿瘤下调CD 23的机制。我们在这里表明，尽管肿瘤细胞和B细胞之间需要直接接触，但这是不够的，因为固定的肿瘤细胞不会诱导相同的CD 23表达降低。我们已经鉴定了IL-10（一种由肿瘤产生的细胞因子）作为导致浆细胞肿瘤诱导的B细胞上的CD 23表达降低的唯一可溶性因子，因为1）IL-10的Ab在体外和体内都防止了浆细胞肿瘤诱导的CD 23损失; 2）这些肿瘤的工程化IL-10阴性变体下调CD 23表达的能力降低; 3）rIL-10单独诱导正常脾B细胞上CD 23表达的部分但显著的降低;和4）加入IL-10和固定的肿瘤细胞与正常脾细胞培养物的混合物将CD 23表达降低至与活肿瘤细胞共培养物中的水平相似的水平。总的来说，这些结果表明，浆细胞肿瘤通过IL-10加上接触介导事件的协调机制下调B细胞上的CD 23表达，并揭示了IL-10在调节B细胞上的CD 23表达中的新作用，这提示在肿瘤存在下宿主B细胞活化。
We and others have previously found that splenic B cells from plasma cell tumor-bearing mice exhibit decreased CD23 expression. In the present study we further examined the mechanism of CD23 down-regulation by plasma cell tumors. We show here that although direct contact is required between the tumor cells and B cells, it is not sufficient, since fixed tumor cells do not induce the same reduction in CD23 expression. We have identified IL-10, a cytokine produce by the tumors, as the sole soluble factor that contributes to decreased CD23 expression on B cells induced by plasma cell tumors because 1) Abs to IL-10 prevent the loss of CD23 induced by plasma cell tumors both in vitro and in vivo; 2) engineered IL-10 negative variants of these tumors are reduced in their ability to down-regulate CD23 expression; 3) rIL-10 alone induces partial, but significant, decreases in CD23 expression on normal splenic B cells; and 4) the addition of IL-10 and fixed tumor cells to cultures of normal splenocytes decreases CD23 expression to levels similar to those in cocultures with live tumor cells. Collectively, these results demonstrate that plasma cell tumors down-regulate CD23 expression on B cells by a coordinate mechanism of IL-10 plus contact-mediated events and reveal a novel role for IL-10 in the regulation of CD23 expression on B cells that is suggestive of host B cell activation in the presence of the tumor.