Chronic lymphocytic leukemia B cells can express CD40 ligand and demonstrate T-cell type costimulatory capacity.
Chronic lymphocytic leukemia B cells can express CD40 ligand and demonstrate T-cell type costimulatory capacity.
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DOI：
10.1182/blood.v91.8.2689.2689_2689_2697
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发表时间：
1998-04
期刊：
影响因子：
20.3
通讯作者：
E. Schattner;J. Mascarenhas;Inna Reyfman;Mary Koshy;C. Woo;S. Friedman;M. Crow
中科院分区：
文献类型：
--
作者：
E. Schattner;J. Mascarenhas;Inna Reyfman;Mary Koshy;C. Woo;S. Friedman;M. Crow
慢性淋巴细胞白血病（CLL）以外周血CD5(+) B细胞克隆扩增为特征。相关的免疫异常包括th细胞功能异常和致病性自身抗体。在大多数情况下，CLL B细胞在培养中不增殖，表达有限的表面抗原，包括CD19、CD20、CD23、CD27、CD40和CD70。在本报告中，我们证明了从CLL病例亚群中新分离的B细胞组成性地表达CD40配体（CD40L, CD154），这是肿瘤坏死因子家族的一员，通常由活化的CD4(+) T细胞表达，并介导T细胞依赖性B细胞增殖和抗体产生。CD40L的表达程度在不同的CLL病例中差异很大。用免疫荧光流式细胞术、RT-PCR和免疫沉淀法检测纯化的CLL B细胞中的CD40L。为了证明CLL B细胞中的CD40L是功能性的，我们使用辐照的CLL细胞刺激共培养的靶非恶性B细胞产生IgG。CLL B细胞诱导正常B细胞产生IgG的程度与纯化T细胞相似，该过程被CD40L单克隆抗体部分抑制。这是首次报道CD40L在b细胞肿瘤中的表达。这些数据提示，在一些CLL患者中，肿瘤细胞中的CD40L可能是正常B细胞产生病理性抗体的一个因素。
Chronic lymphocytic leukemia (CLL) is characterized by a clonal expansion of CD5(+) B cells in the peripheral blood. Associated immune aberrations include abnormal Th-cell function and pathogenic autoantibodies. Under most circumstances, CLL B cells do not proliferate in culture and express a limited repertoire of surface antigens, including CD19, CD20, CD23, CD27, CD40, and CD70. In this report, we demonstrate that freshly isolated B cells from a subset of CLL cases constitutively express CD40 ligand (CD40L, CD154), a member of the tumor necrosis factor family which is normally expressed by activated CD4(+) T cells and mediates T-cell-dependent B-cell proliferation and antibody production. The degree of CD40L expression varied considerably among the CLL cases examined. CD40L was detected in purified CLL B cells by immunofluorescence flow cytometry, by RT-PCR, and by immunoprecipitation. To demonstrate that CD40L in the CLL B cells is functional, we used irradiated CLL cells to stimulate IgG production by target, nonmalignant B cells in coculture. The CLL B cells induced IgG production by normal B cells to a similar degree as did purified T cells in a process which was partially inhibited by monoclonal antibody to CD40L. This is one of the first reports of CD40L expression in a B-cell tumor. The data suggest that CD40L in the tumor cells may be a factor in the generation of pathologic antibodies by normal B cells in some patients with CLL.