Clodi K, Asgary Z, Zhao S, Kliche K O, Cabanillas F, Andreeff M, Younes A
Department of Molecular Hematology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Br J Haematol. 1998 Oct;103(1):270-5. doi: 10.1046/j.1365-2141.1998.01031.x.
CD40 ligand (CD40L) is involved in the T-cell-dependent regulation of B-cell growth and survival and can rescue normal germinal centre B cells and several types of malignant B cells from apoptosis in vitro. We have previously reported that serum of patients with chronic lymphocytic leukaemia contained elevated levels of biologically active soluble CD40L (sCD40L). Whether an augmented CD40L pathway exists in patients with other types of B-cell lymphoid malignancies and the source of native sCD40L in these patients is currently unknown. Using a sensitive ELISA assay, soluble CD40L (sCD40L) was detected in the sera of both healthy individuals and patients with haematological malignancies; however, its level was significantly elevated only in patients with B-cell lymphomas (P<0.0001). Several types of malignant B cells coexpressed CD40 and CD40L proteins, and CD40L mRNA was detected in purified resting malignant B cells. The dual expression of CD40 and CD40L in B cells and the presence of native sCD40L in human serum suggest that a direct T-B-cell contact may not be required for CD40L delivery to B cells. This data raises the possibility that an autocrine cytokine loop involving CD40L may contribute to the growth regulation of benign and malignant B cells in vivo.
CD40配体(CD40L)参与T细胞依赖的B细胞生长和存活调节,并且在体外可使正常生发中心B细胞和几种恶性B细胞免于凋亡。我们之前报道过,慢性淋巴细胞白血病患者的血清中生物活性可溶性CD40L(sCD40L)水平升高。目前尚不清楚其他类型B细胞淋巴瘤患者是否存在增强的CD40L途径以及这些患者体内天然sCD40L的来源。使用灵敏的ELISA检测法,在健康个体和血液系统恶性肿瘤患者的血清中均检测到了可溶性CD40L(sCD40L);然而,仅在B细胞淋巴瘤患者中其水平显著升高(P<0.0001)。几种恶性B细胞共表达CD40和CD40L蛋白,并且在纯化的静止恶性B细胞中检测到了CD40L mRNA。B细胞中CD40和CD40L的双重表达以及人血清中天然sCD40L的存在表明,CD40L传递至B细胞可能不需要T-B细胞直接接触。该数据增加了一种可能性,即涉及CD40L的自分泌细胞因子环可能在体内对良性和恶性B细胞的生长调节起作用。