The Regulation of Inherently Autoreactive VH4-34-Expressing B Cells in Individuals Living in a Malaria-Endemic Area of West Africa.
The Regulation of Inherently Autoreactive VH4-34-Expressing B Cells in Individuals Living in a Malaria-Endemic Area of West Africa.
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DOI：
10.4049/jimmunol.1600491
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发表时间：
2016-11-15
期刊：
影响因子：
--
通讯作者：
Pierce SK
中科院分区：
文献类型：
--
作者：
Hart GT;Akkaya M;Chida AS;Wei C;Jenks SA;Tipton C;He C;Wendel BS;Skinner J;Arora G;Kayentao K;Ongoiba A;Doumbo O;Traore B;Narum DL;Jiang N;Crompton PD;Sanz I;Pierce SK
恶性疟疾是一种致命的传染病，抗体在自然获得性免疫中起着关键作用。然而，目前对疟疾引起的抗体的特异性和性质只有部分了解。自身反应性和多反应性是几种感染中抗体反应的共同特征，已被认为有助于有效的病原体特异性抗体反应。在这里，我们报道了在西非恶性疟流行区的成人和儿童中，B细胞表达固有的自身反应性VH4-34重链(由9G4单抗鉴定)和9G4+血浆免疫球蛋白的调节。9G4+外周血CD19+B细胞的频率在美国成年人和非洲成年人和儿童中相似。然而，与美国成年人相比，非洲儿童和成人的经典和非典型记忆B细胞室中出现了更多的9G4+B细胞。9G4+免疫球蛋白水平在急性热性疟疾后升高，但不随年龄增加，因为体液免疫是获得的或与急性疾病的保护相关。尽管部分9G4+B细胞获得了非典型和经典记忆B细胞的表型，并且与所有其他VHS相比，9G4+IgG含有等量的体细胞超突变，这是对抗原刺激反应的二次抗体谱多样化的特征。确定疟疾中9G4+B细胞和9G4+免疫球蛋白的来源和功能可能有助于更好地理解自身反应性在传染病中的不同作用。
Plasmodium falciparum malaria is a deadly infectious disease in which antibodies play a critical role in naturally acquired immunity. However, at present the specificity and nature of antibodies elicited in response to malaria is only partially understood. Autoreactivity and polyreactivity are common features of antibody responses in several infections and have been suggested to contribute to effective pathogen-specific antibody responses. Here we report on the regulation of B cells expressing the inherently autoreactive VH4-34 heavy chain (identified by the 9G4 monoclonal antibody) and 9G4+ plasma IgG in adults and children living in a P. falciparum malaria-endemic area in West Africa. The frequency of 9G4+ peripheral blood CD19+ B cells was similar in U.S. adults and African adults and children. However, more 9G4+ B cells appeared in classical and atypical memory B cell compartments in African children and adults as compared to U.S. adults. The levels of 9G4+ IgG increased following acute febrile malaria, but did not increase with age as humoral immunity is acquired or correlate with protection from acute disease. This was the case even though a portion of 9G4+ B cells acquired phenotypes of atypical and classical memory B cells and 9G4+ IgG contained equivalent numbers of somatic hypermutations as compared to all other VHs, a characteristic of secondary antibody repertoire diversification in response to antigen stimulation. Determining the origin and function of 9G4+ B cells and 9G4+ IgG in malaria may contribute to a better understanding of the varied roles of autoreactivity in infectious diseases.
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影响因子：
56.9
作者：
Haynes, BF;Fleming, J;Alam, SM
通讯作者：
Alam, SM
DOI：
10.1073/pnas.1417683112
发表时间：
2015-02-24
影响因子：
11.1
作者：
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通讯作者：
Kleinstein, Steven H.
影响因子：
15.3
作者：
Moir, Susan;Ho, Jason;Fauci, Anthony S.
通讯作者：
Fauci, Anthony S.
影响因子：
27.4
作者：
Isenberg, DA;McClure, C;Stevenson, F
通讯作者：
Stevenson, F
影响因子：
15.9
作者：
Cappione, A;Anolik, JH;Sanz, I
通讯作者：
Sanz, I