Ruzek M C, Billadeau D, Mathur A
Department of Microbiology, University of Minnesota, Minneapolis 55455, USA.
J Immunol. 1996 Mar 15;156(6):2124-32.
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.
我们和其他人之前发现，来自患有浆细胞瘤小鼠的脾脏B细胞表现出CD23表达降低。在本研究中，我们进一步研究了浆细胞瘤下调CD23的机制。我们在此表明，虽然肿瘤细胞和B细胞之间需要直接接触，但这并不充分，因为固定的肿瘤细胞不会诱导相同程度的CD23表达降低。我们已确定IL-10，一种由肿瘤产生的细胞因子，是导致浆细胞瘤诱导的B细胞上CD23表达降低的唯一可溶性因子，原因如下：1）抗IL-10抗体可在体外和体内阻止浆细胞瘤诱导的CD23丢失；2）这些肿瘤的工程化IL-10阴性变体下调CD23表达的能力降低；3）单独的重组IL-10可诱导正常脾脏B细胞上的CD23表达出现部分但显著的降低；4）将IL-10和固定的肿瘤细胞添加到正常脾细胞培养物中，可使CD23表达降低至与活肿瘤细胞共培养时的水平。总体而言，这些结果表明浆细胞瘤通过IL-10加接触介导事件的协同机制下调B细胞上的CD23表达，并揭示了IL-10在调节B细胞上CD23表达中的新作用，这提示在肿瘤存在的情况下宿主B细胞被激活。
