Immunophenotypic analysis of the Kaposi sarcoma herpesvirus (KSHV; HHV-8)-infected B cells in HIV+ multicentric Castleman disease (MCD)
Immunophenotypic analysis of the Kaposi sarcoma herpesvirus (KSHV; HHV-8)-infected B cells in HIV+ multicentric Castleman disease (MCD)
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DOI：
10.1111/j.1365-2559.2008.03144.x
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发表时间：
2008-11-01
期刊：
影响因子：
6.4
通讯作者：
Knowles, D. M.
中科院分区：
文献类型：
--
作者：
Chadburn, A.;Hyjek, E. M.;Knowles, D. M.
目的：卡波西肉瘤疱疹病毒（KSHV）与卡波西肉瘤、经典和腔外原发性渗出性淋巴瘤（PEL; EC-PEL）和多中心Castleman病（MCD）在病因学上相关，这些实体优先发生在HIV感染者中。HIV相关的PELs/EC-PELs的特征表明KSHV感染的恶性细胞起源于B细胞分化的前终末阶段。然而，仅对HIV+ MCD进行了有限的表型研究，包括含PR结构域1和锌指结构域/B淋巴细胞诱导成熟蛋白1（PRDM 1/BLIMP 1）的表型研究，PRDM 1/BLIMP 1是终末B细胞分化的关键调节因子。目的是表征KSHV感染的细胞在17例HIV+ MCD。方法和结果：采用双重免疫组化和荧光化学-原位杂交的特点，KSHV感染的细胞在MCD的结果进行了比较的表型配置文件的39个PELs/EC-PELs和7个PEL细胞系。而MCD和恶性KSHV+ PEL细胞中KSHV感染细胞的免疫表型相似（PAX 5，Bcl-6-; PRDM 1/BLIMP 1，IRF 4/MUM 1 +; Ki 67+），MCD KSHV感染的细胞不同，因为它们表达OCT 2，细胞质λ免疫球蛋白; CD 27表达;缺乏CD 138;并且是EB病毒阴性的。尽管PEL和MCD均来源于KSHV感染的终末前分化的B细胞，但这些发现以及先前报道的遗传学研究表明，HIV+ MCD可能来源于滤泡外B细胞，而PEL可能来源于穿过生发中心的细胞。
Aims: Kaposi sarcoma herpesvirus (KSHV) is aetiologically related to Kaposi sarcoma, classical and extracavitary primary effusion lymphoma (PEL; EC-PEL) and multicentric Castleman disease (MCD), entities preferentially occurring in HIV-infected individuals. Characterization of HIV-associated PELs/EC-PELs suggests that the KSHV-infected malignant cells originate from a pre-terminal stage of B-cell differentiation. However, only limited phenotypic studies have been performed on HIV+ MCD, including for PR domain containing 1 with zinc finger domain/B lymphocyte-induced maturation protein 1 (PRDM1/BLIMP1), a key regulator of terminal B-cell differentiation. The aim was to characterize KSHV-infected cells in 17 cases of HIV+ MCD.Methods and results: Double immunohistochemistry and immunohistochemistry-in situ hybridization were used to characterize the KSHV-infected cells in MCD; the results were compared with the phenotypic profiles of 39 PELs/EC-PELs and seven PEL cell lines. Whereas the immunophenotype of KSHV-infected cells in MCD and malignant KSHV+ PEL cells was similar (PAX5, Bcl-6-; PRDM1/BLIMP1, IRF4/MUM1+; Ki67+), the MCD KSHV-infected cells differed, as they expressed OCT2, cytoplasmic lambda immunoglobulin; variably expressed CD27; lacked CD138; and were Epstein-Barr virus negative.Conclusions: Although both PEL and MCD originate from KSHV-infected pre-terminally differentiated B cells, these findings, with previously reported genetic studies, indicate HIV+ MCD may arise from extrafollicular B cells, whereas PELs may originate from cells that have traversed the germinal centre.