Antibodies to CD40 prevent Epstein-Barr virus-mediated human B-cell lymphomagenesis in severe combined immune deficient mice given human peripheral blood lymphocytes.
Antibodies to CD40 prevent Epstein-Barr virus-mediated human B-cell lymphomagenesis in severe combined immune deficient mice given human peripheral blood lymphocytes.
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在给予人外周血淋巴细胞的严重联合免疫缺陷小鼠中，CD40 抗体可预防 Epstein-Barr 病毒介导的人 B 细胞淋巴瘤发生。
作者：
W. Murphy;S. Funakoshi;M. Beckwith;S. E. Rushing;D. Conley;R. Armitage;W. Fanslow;H. Rager;D. Taub;F. Ruscetti
CD 40在正常和肿瘤性B淋巴细胞上均表达。通过CD 40的信号转导在体外已被证明对正常B细胞具有刺激作用，并且对EB病毒（EBV）诱导的B细胞淋巴瘤系和来自侵袭性组织学淋巴瘤患者的一些其它细胞系具有抑制作用。以前已经证明，将正常人外周血淋巴细胞（huPBL）从EBV血清阳性供体转移到严重联合免疫缺陷（SCID）小鼠中会导致人B细胞淋巴瘤的产生。这些肿瘤与移植后或免疫缺陷情况下临床上可能出现的高度侵袭性的EB病毒诱导的淋巴瘤相似。用抗CD 40或抗CD 20单克隆抗体（MoAb）治疗huPBL-SCID嵌合小鼠显著延迟了EBV诱导的B细胞淋巴瘤的发展。然而，两种单克隆抗体的作用机制不同。与未接受治疗的小鼠相比，抗CD 40治疗防止了淋巴瘤的产生，同时仍然允许在huPBL-SCID小鼠中进行功能性人B细胞移植，所有小鼠都死于淋巴瘤。相比之下，抗CD 20治疗显著抑制了SCID受者中的总人B细胞植入，这是不存在淋巴瘤的原因。在体外试验中，检测EBV对人B细胞的转化也表明，抗CD 40抗体可直接抑制EBV转化，而抗CD 20抗体则无作用。因此，抗-CD 40发挥选择性作用以允许正常人B细胞的植入并防止EBV淋巴瘤的出现。因此，通过抗体或其生理配体刺激CD 40可在预防EBV诱导的B淋巴瘤中具有重要的临床用途，所述B淋巴瘤可在EBV血清阳性个体在移植后或在免疫缺陷状态（例如获得性免疫缺陷综合征）中接受免疫抑制方案时出现。
CD40 is expressed on both normal and neoplastic B lymphocytes. Signal transduction through CD40 in vitro has been shown to exert stimulatory effects on normal B cells and inhibitory effects on Epstein-Barr virus (EBV)-induced B-cell lymphoma lines and some other cell lines derived from patients with aggressive histology lymphoma. The transfer of normal human peripheral blood lymphocytes (huPBL) from EBV-seropositive donors into severe combined immune deficient (SCID) mice has been previously shown to result in the generation of human B-cell lymphomas. These tumors are similar to the highly aggressive EBV-induced lymphomas that can arise clinically after transplantation or in the setting of immunodeficiency. Treatment of huPBL-SCID chimeric mice with anti-CD40 or anti-CD20 monoclonal antibodies (MoAb) significantly delayed the development of EBV-induced B-cell lymphoma. However, the effects of the two MoAb were mechanistically distinct. Anti-CD40 treatment prevented lymphoma generation, while still allowing for functional human B-cell engraftment in the huPBL-SCID mice compared with mice receiving no treatment, all of which succumbed to lymphoma. By contrast, treatment with anti-CD20 significantly inhibited total human B-cell engraftment in the SCID recipients, which accounted for the absence of lymphomas. In vitro assays examining the transformation of human B cells by EBV also indicated that anti-CD40 could directly inhibit EBV-transformation, whereas anti-CD20 antibodies had no effect. Thus, anti-CD40 exerts selective effects to allow for the engraftment of normal human B cells and prevent the emergence of EBV lymphomas. Stimulation of CD40 by antibodies or its physiologic ligand may, therefore, be of significant clinical use in the prevention of EBV-induced B lymphomas that may arise when EBV-seropositive individuals receive immunosuppressive regimens after transplantation or in immune deficiency states, such as acquired immune deficiency syndrome.
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严重联合免疫缺陷小鼠中 Epstein-Barr 病毒诱导的人 B 淋巴细胞增殖性疾病的克隆特征。
DOI：
--
发表时间：
1993
期刊：
The American journal of pathology
影响因子：
--
作者：
Nakamine,H;Masih,AS;Okano,M;Taguchi,Y;Pirruccello,SJ;Davis,JR;Mahloch,ML;Beisel,KW;Kleveland,K;Sanger,WG
通讯作者：
Sanger,WG
通过识别 T 细胞抗原受体复合物的抗体抑制人类 T 细胞的生长。
DOI：
--
发表时间：
1987
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Breitmeyer,JB;Oppenheim,SO;Daley,JF;Levine,HB;Schlossman,SF
通讯作者：
Schlossman,SF
CD40 在人 B 细胞分化中的免疫调节作用。
DOI：
--
发表时间：
1993
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Splawski,JB;Fu,SM;Lipsky,PE
通讯作者：
Lipsky,PE
影响因子：
10.3
作者：
BECKWITH, M;LONGO, DL;URBA, WJ
通讯作者：
URBA, WJ