Bcl-6 protein expression in normal and neoplastic lymphoid tissues.
Bcl-6 protein expression in normal and neoplastic lymphoid tissues.
复制标题
Bcl-6 蛋白在正常和肿瘤淋巴组织中表达。
作者：
B. Falini;M. Fizzotti;S. Pileri;A. Liso;L. Pasqualucci;L. Flenghi
人类bcl - 6基因在约30%的弥漫性大B细胞淋巴瘤（DLCL - B）中发生重排，它编码一种含706个氨基酸的克鲁佩尔型锌指蛋白。为了在蛋白质水平研究bcl - 6基因的表达，用一种对应于bcl - 6氨基末端区域（氨基酸3 - 484）的重组蛋白免疫Balb/c小鼠，产生了两种针对人类bcl - 6蛋白的单克隆抗体（PG - B6a和PG - B6p）。PG - B6a（a = 禽类）识别最保守的bcl - 6表位（在许多动物物种中表达，包括禽类）。PG - B6p（p = 石蜡）与bcl - 6的一个对固定剂有一定抗性且在微波加热的石蜡切片上可检测到的表位发生反应。在免疫细胞化学中，bcl - 6以微颗粒状或弥漫状定位于细胞核。bcl - 6的强核表达主要在正常生发中心B细胞中检测到，而套细胞和边缘区B细胞以及浆细胞和骨髓B细胞前体不表达bcl - 6。这些免疫组织学发现强烈提示bcl - 6可能作为生发中心相关功能的调节因子发挥作用。所有单克隆抗体都能对滤泡性淋巴瘤、DLCL - B和伯基特淋巴瘤的肿瘤细胞进行染色。在DLCL - B中，bcl - 6的表达与bcl - 6基因重排无关，且与其他标志物的表达或增殖指数无关。在低级别B细胞淋巴瘤中，bcl - 6的免疫染色有助于区分B - CLL中的增殖中心（bcl - 2 + /bcl - 6 - ）和套细胞淋巴瘤中被困的生发中心（bcl - 2 - /bcl - 6 + ）。在结节性淋巴细胞为主型霍奇金病（NLPHD）的肿瘤（L&H）细胞中始终检测到bcl - 6的强核阳性。这些结果进一步支持了NLPHD是一种在组织发生上独特的（生发中心衍生的）霍奇金病亚型这一概念。值得注意的是，在NLPHD中靠近L&H细胞并环绕其形成花环的反应性CD3 + /CD4 + T细胞的细胞核也呈强bcl - 6阳性，但缺乏CD40配体（CD40L）表达。这种染色模式明显不同于经典霍奇金病，经典霍奇金病的细胞背景由呈现bcl - 6 - /CD40L + 表型的CD3 + /CD4 + T细胞组成。上述免疫组织学发现提示：（a）bcl - 6可能在调节生发中心内发生的B细胞分化步骤中起作用；（b）由重排导致的bcl - 6表达失调可能有助于B淋巴瘤的发生；（c）bcl - 6可能参与NLPHD的发病机制。
The human bcl-6 gene, which is rearranged in about 30% of diffuse large B-cell lymphomas (DLCL-B), encodes for a Kruppel-type zinc finger protein of 706 amino acids. In order to investigate the expression of the bcl-6 gene at the protein level, two monoclonal antibodies (PG-B6a and PG-B6p) directed against the human bcl-6 protein were generated by immunizing Balb/c mice with a recombinant protein corresponding to the amino-terminal region (amino acids 3-484) of bcl-6. PG-B6a (a = avian) recognized the most conserved bcl-6 epitope (expressed in many animal species, including avian). PG-B6p (p = paraffin) reacted with an epitope of bcl-6 partially resistant to fixatives and detectable on microwave-heated paraffin sections. At immunocytochemistry, bcl-6 localized in the nucleus with a microgranular or diffuse pattern. Strong nuclear expression of bcl-6 was mainly detected in normal germinal-center B-cells, whereas mantle- and marginal-zone B cells, as well as plasma cells and marrow B-cell precursors, did not express bcl-6. These immunohistological findings strongly suggest that bcl-6 may play a role as a regulator of germinal-center related functions. All MoAbs stained neoplastic cells of follicular lymphomas, DLCL-B, and Burkitt's lymphomas. In DLCL-B, bcl-6 expression was independent of bcl-6 gene rearrangements and did not correlate with expression of other markers or the proliferation index. Among low-grade B-cell lymphomas, immunostaining for bcl-6 proved useful for differentiating proliferation centers in B-CLL (bcl-2+/bcl-6-) from trapped germinal centers in mantle-cell lymphomas (bcl-2-/bcl-6+). Strong nuclear positivity for bcl-6 was consistently detected in tumor (L&H) cells of nodular, lymphocyte-predominant Hodgkin's disease (NLPHD). These results further support the concept that NLPHD is a histogenetically distinct (germinal-center derived) subtype of HD. Notably, the nuclei of reactive CD3+/ CD4+ T cells near to and rosetting around L&H cells in NLPHD were also strongly bcl-6+, but lacked CD40 ligand (CD40L) expression. This staining pattern clearly differed from that of classic HD, whose cellular background was made up of CD3+/CD4+ T cells showing the bcl-6-/CD40L+ phenotype. The above immunohistological findings suggest that (a) bcl-6 may play a role in regulating B-cell differentiation step(s) occurring within germinal centers; (b) deregulated bcl-6 expression caused by rearrangements may contribute to B-lymphomagenesis; (c) bcl-6 is possibly involved in the pathogenesis of NLPHD.
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影响因子：
56.9
作者：
YE, BH;LISTA, F;DALLAFAVERA, R
通讯作者：
DALLAFAVERA, R
影响因子：
20.3
作者：
CATTORETTI, G;CHANG, CC;DALLAFAVERA, R
通讯作者：
DALLAFAVERA, R
DOI：
10.1073/pnas.88.13.5857
发表时间：
1991-07-01
影响因子：
11.1
作者：
NEIMAN, PE;THOMAS, SJ;LORING, G
通讯作者：
LORING, G
影响因子：
11.4
作者：
Ye, BH;Chaganti, S;DallaFavera, R
通讯作者：
DallaFavera, R
bcl-6 基因重排作为弥漫性大细胞淋巴瘤的预后标志物。
DOI：
10.1056/nejm199407143310202
发表时间：
1994
期刊：
The New England journal of medicine
影响因子：
--
作者：
Offit,K;LoCoco,F;Louie,DC;Parsa,NZ;Leung,D;Portlock,C;Ye,BH;Lista,F;Filippa,DA;Rosenbaum,A
通讯作者：
Rosenbaum,A