Expression of activation-induced cytidine deaminase in human B-cell non-Hodgkin lymphomas
Expression of activation-induced cytidine deaminase in human B-cell non-Hodgkin lymphomas
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DOI：
10.1182/blood-2002-08-2424
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发表时间：
2003-05-01
期刊：
影响因子：
20.3
通讯作者：
Parwaresch, R
中科院分区：
文献类型：
--
作者：
Greeve, J;Philipsen, A;Parwaresch, R
激活诱导的胞苷脱氨酶 (AID) 可诱导 B 淋巴细胞中的体细胞超突变 (SHM)、类别转换重组 (CSR) 和免疫球蛋白基因转换。在此，我们首次报告了 AID 在健康人 B 淋巴细胞和 B 细胞非霍奇金淋巴瘤 (B-NHL) 中的表达。人类中AID mRNA的表达仅限于CD19(+)CD38(+)IgD(-)生发中心细胞，即CD10(+)CD38(+)CD44(-)中心母细胞。 CD40-L 和 IL-4 体外刺激初始人类 B 细胞后，AID mRNA 仅在 48 小时内被强烈诱导。在一项对人类 B-NHL-AID 的调查中发现，B-NHL-AID 在滤泡性淋巴瘤和弥漫性大 B 细胞淋巴瘤中组成型表达，但在 B 前体淋巴细胞白血病、套细胞淋巴瘤和浆细胞骨髓瘤中不存在。在 B 细胞慢性淋巴白血病、免疫细胞瘤和 MALT 结外边缘区 B 细胞淋巴瘤中，AID mANA 仅在某些样本中表达。在滤泡性淋巴瘤和弥漫性大 B 细胞淋巴瘤中，AID mRNA 的表达与免疫球蛋白重链基因可变区外显子中 SHM 的存在一致。在人类 B-NHL 中，AID mRNA 被剪接成 4 种不同的变体，但不包含点突变。因此，在健康 B 细胞发育过程中受到高度调控的 AID 在人生发中心 B-NHL 和非生发中心 B-NHL 亚群中组成型表达。 AID 的这种组成型表达可能促进 B-NHL 中的非法 DNA 重组和体细胞突变。 (C) 2003 年，美国血液学会。
Activation-induced cytidine deaminase (AID) induces somatic hypermutation (SHM), class switch recombination (CSR), and immunoglobulin gene conversion in B-lymphocytes. Here we report for the first time the expression of AID in healthy human B-lymphocytes and in B-cell non-Hodgkin lymphomas (B-NHL). AID mRNA expression in humans is restricted to the CD19(+)CD38(+)IgD(-) germinal center cells, namely the CD10(+)CD38(+)CD44(-) centro-blasts. After in vitro stimulation of naive human B cells by CD40-L and IL-4, AID mRNA is strongly induced for only 48 hours. In a survey of human B-NHL-AID was found to be constitutively expressed in follicular lymphoma and in diffuse large B-cell lymphoma but to be absent in B-precursor lymphoblastic leukemia, in mantle cell lymphoma, and in plasmia cell myeloma. In B-cell chronic lymphatic leukemia, in immunocytoma, and in extra-nodal marginal zone B-cell lymphoma of MALT, AID mANA was expressed only in some samples. In follicular lymphoma and diffuse large B-cell lymphoma, the expression of AID mRNA was coincident with the presence of SHM in the variable region exons of the immunoglobulin heavy-chain gene. In human B-NHL, the AID mRNA is spliced into 4 different variants but does riot contain point, mutations. Thus AID, which is highly regulated during healthy B-cell development, is constitutively expressed in human germinal center B-NHL and in subsets of nongerminal center B-NHL. This constitutive expression of AID may promote illegitimate DNA recombinations and somatic mutations in B-NHL. (C) 2003 by The American Society of Hematology.