CD38 expression distinguishes two groups of B-cell chronic lymphocytic leukemias with different responses to anti-IgM antibodies and propensity to apoptosis.
CD38 expression distinguishes two groups of B-cell chronic lymphocytic leukemias with different responses to anti-IgM antibodies and propensity to apoptosis.
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DOI：
10.1182/blood.v88.4.1365.bloodjournal8841365
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发表时间：
1996-08
期刊：
影响因子：
20.3
通讯作者：
S. Zupo;Laura Isnardi;M. Megna;R. Massara;Fabio Malavasi;M. Dono;Elisabetta Cosulich;M. Ferrarini
中科院分区：
文献类型：
--
作者：
S. Zupo;Laura Isnardi;M. Megna;R. Massara;Fabio Malavasi;M. Dono;Elisabetta Cosulich;M. Ferrarini
研究了20例未经治疗的慢性淋巴细胞白血病（B- cll）患者B细胞中CD38的表达情况。6例（I组）细胞表达丰富CD38（相对荧光强度范围6 ~ 15），其余（II组）细胞表达低至不表达CD38（相对荧光强度范围0 ~ 3）。I组患者细胞暴露于山羊抗人mu链抗体（Ga mu-ab）导致细胞内游离Ca2+浓度（[Ca2+] I）升高，随后发生凋亡。相比之下，II组细胞暴露于Ga mu-ab后，没有出现[Ca2+]i水平升高、程序性细胞死亡或细胞增殖。两组B-CLL细胞表面IgM表达无差异。正常外周血B细胞，表达低至缺失CD38，能够动员[Ca2+]i，并在暴露于Ga mu-ab后增殖。收集到的数据表明，尽管I组B-CLL细胞能够转导IgM交联传递的信号，但该途径在II组B-CLL细胞中严重受损。然而，与在正常循环B细胞中观察到的不同，用Ga mu-ab刺激I组细胞导致凋亡而不是增殖。在i组B-CLL细胞中，CD38似乎没有直接参与Ga mu-ab诱导的[Ca2+]i动员，因为它们暴露于抗CD38单克隆抗体不能引起[Ca2+]i动员或阻断Ga mu-ab诱导的[Ca2+]i反应。这些数据表明，CD38表达鉴定出具有明确功能特性的B-CLL细胞的一个特定亚群，包括发生凋亡的倾向。
The expression of CD38 by B cells chronic lymphocytic leukemia (B-CLL) was studied in 20 untreated patients. The cells expressed abundant CD38 (relative fluorescence intensity range, 6 to 15) in 6 cases (group I patients), whereas CD38 expression was low to absent (relative fluorescence intensity range, 0 to 3) in the remaining cases (group II patients). Exposure of the cells from group I patients to goat antihuman mu chain antibodies (Ga mu-ab) resulted in the elevation of intracellular free Ca2+ concentration([Ca2+]i) followed by apoptosis. In contrast, exposure of group II cells to Ga mu-ab was not followed by increased levels of [Ca2+]i, programmed cell death or cell proliferation. No differences in the expression of surface IgM were noted in the two groups of B-CLL cells. Normal peripheral blood B cells, which expressed low to absent CD38, were capable of mobilizing [Ca2+]i and of proliferating after exposure to Ga mu-ab. The collected data suggest that, although group I B-CLL cells were able to transduce the signals delivered by IgM crosslinking, this pathway was severely impaired in group II B-CLL cells. However, unlike that observed in normal circulating B cells, stimulation of group I cells with Ga mu-ab resulted in apoptosis rather than proliferation. CD38 did not appear to be directly involved in [Ca2+]i mobilization induced by Ga mu-ab in group I B-CLL cells because their exposure to anti-CD38 monoclonal antibodies failed to cause [Ca2+]i mobilization or to block the [Ca2+]i response induced by Ga mu-ab. These data indicate that CD38 expression identified a particular subset of B-CLL cells with defined functional properties, including the propensity to undergo apoptosis.