Regeneration of Natural Antibody Repertoire After Massive Ablation of Lymphoid System: Robust Selection Mechanisms Preserve Antigen Binding Specificities1

Regeneration of Natural Antibody Repertoire After Massive Ablation of Lymphoid System: Robust Selection Mechanisms Preserve Antigen Binding Specificities1
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大规模消融淋巴系统后天然抗体库的再生:稳健的选择机制保留抗原结合特异性1

DOI:
--
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发表时间:
2002
影响因子:
4.4
通讯作者:
A. Coutinho
A. Coutinho
中科院分区:
医学2区
文献类型:
--
作者:
A. Nóbrega;B. Stransky;N. Nicolas;A. Coutinho

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天然抗体(NAb)是存在于健康脊椎动物血清和体液中的免疫球蛋白,没有任何先前的有意免疫。NAb通常表现出自身反应性,但也在免疫中发挥重要作用,是对抗感染性微生物的第一道防线。我们先前分析了正常小鼠的天然血清IgM Ab库,表征其与数百/数千个自身抗原的反应性;观察到不同个体之间的显著相似性,并且发现在成年期间稳定保持的NAb的许多反应性在生命早期建立,这意味着该时期是NAb库选择生理学中的关键时间窗口。在这里报道的工作中,进行了实验,以解决正常淋巴细胞个体发育的成人NAb库的形成和稳定性的作用。用γ射线照射成年小鼠可促进淋巴系统的大量破坏,骨髓或胎肝接种物可促进造血组织的再生。在骨髓或胎肝嵌合体动物中,在γ-照射后60天跟踪NAb库再生。与数百/数千个自身抗原的血清IgM反应性的分析表明,NAb库再生的大部分其原始格式后,大量破坏淋巴隔室,自身反应性库的选择作为一个强大的生物过程的特征。数据还显示,NAb库的再生在胎肝和骨髓嵌合体中类似地发生,尽管后者动物重建其CD 5 + B1细胞区室较差,表明B1细胞对于天然Ab再生不是必需的。
Natural Abs (NAbs) are Igs present in the serum and body fluids of healthy vertebrate animals, without any previous intentional immunization. NAbs often exhibit autoreactivity but also play an essential role in immunity, being a first line of defense against infectious microorganisms. We have previously analyzed the natural serum IgM Ab repertoire of normal mice, characterizing their reactivity with hundreds/thousands of self Ags; a significant similarity among different individuals was observed, and it was found that many reactivities of NAbs stably kept during adulthood were established early in life, implicating that period as a critical time window in the physiology of NAb repertoire selection. In the work reported here, experiments were conducted to address the role of normal lymphocyte ontogeny to the formation and stability of adult NAb repertoire. The massive destruction of the lymphoid system was promoted in adult mice with gamma-irradiation, and regeneration of hemopoietic tissues was granted by bone marrow or fetal liver inoculum. NAb repertoire regeneration was followed for 60 days after gamma-irradiation in bone marrow or fetal liver chimeric animals. The analysis of serum IgM reactivity with hundreds/thousands of self Ags showed that the NAb repertoire regenerated most of its original format after massive destruction of lymphoid compartments, characterizing autoreactive repertoire selection as a robust biological process. The data also show that regeneration of the NAb repertoire occurred similarly in fetal liver and bone marrow chimeras, although the latter animals poorly reconstituted their CD5+ B1 cell compartment, suggesting that B1 cells are not essential for natural Ab regeneration.
DOI: 10.1016/s1074-7613(00)80157-0
发表时间: 2000-01-01
期刊: IMMUNITY
影响因子: 32.4
作者:
Martin, F;Kearney, JF
通讯作者: Kearney, JF
正常小鼠中免疫前 B 细胞库的优先自身抗体反应性。
DOI: --
发表时间: 1988
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Souroujon,M;White-Scharf,ME;Andreschwartz,J;Gefter,ML;Schwartz,RS
通讯作者: Schwartz,RS
DOI: 10.1073/pnas.81.8.2494
发表时间: 1984-01-01
期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子: --
作者:
HAYAKAWA, K;HARDY, RR;HERZENBERG, LA
通讯作者: HERZENBERG, LA
DOI: 10.1016/s1074-7613(00)80060-6
发表时间: 1999-05-01
期刊: IMMUNITY
影响因子: 32.4
作者:
Benedict, CL;Kearney, JF
通讯作者: Kearney, JF