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查巴迪疟原虫疟疾早期和晚期血液阶段脾脏B细胞区室的特征分析

Characterization of the spleen B-cell compartment at the early and late blood-stage Plasmodium chabaudi malaria.

作者信息

Castillo-Méndez S I, Zago C A, Sardinha L R, Freitas do Rosário A P, Alvarez J M, D'Império Lima M R

机构信息

Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.

出版信息

Scand J Immunol. 2007 Aug-Sep;66(2-3):309-19. doi: 10.1111/j.1365-3083.2007.01972.x.

Abstract

Polyclonal B-cell activation is a feature of the early spleen cell response to blood-stage Plasmodium chabaudi malaria. Immunity to blood-stage malaria is guaranteed by the generation of B cells able to produce parasite-specific antibodies mainly from the immunoglobulin (Ig)G2a isotype. In the present study, we characterized the spleen B-cell compartment during blood-stage P. chabaudi infection. The numbers of B220(+) and B220(LOW) CD138(+) (plasma) cells increased sharply between days 4 and 7 post-infection (p.i.). At this time B220(+) cells expressed surface (s)IgM, but nearly all B220(LOW) CD138(+) cells showed concomitantly intracellular (i)IgM and IgG2a. Both follicular and marginal zone B cells were activated expressing high amounts of CD69. At day 40 p.i., B220(LOW) CD138(+) cell population was still increased but, differently from acute infection, 61.1% of these cells were positive for iIgG2a while only 14.2% expressed iIgM. Moreover, at days 20 and 40 p.i., 29.2% and 13.0% of B220(+) cells expressed sIgG2a, respectively. According to cell size and expression of CD80, CD86, CD11b, CD44 and CD38, B220(+) sIgG2a(+) cells had a phenotype characteristic of activated/memory B cells. Furthermore, 14.1% of B220(+) sIgG2a(+) cells at day 30 p.i. expressed a marginal zone B-cell phenotype. Importantly, B cells from 40-day-infected mice were very efficient in presenting parasite antigens leading to proliferation of both CD4(+) and CD8(+) cells. Our results contribute for understanding the dynamics of B cells during P. chabaudi infection, underlying the mechanisms of antigen presentation and antibody production, which are essential for the acquisition of protective immunity against malaria.

摘要

多克隆B细胞激活是脾脏细胞对血液期恰氏疟原虫疟疾早期反应的一个特征。对血液期疟疾的免疫是由能够产生主要为免疫球蛋白(Ig)G2a同种型的寄生虫特异性抗体的B细胞的产生来保证的。在本研究中,我们对恰氏疟原虫血液期感染期间的脾脏B细胞区室进行了表征。感染后(p.i.)第4天至第7天,B220(+)和B220(LOW) CD138(+)(浆)细胞数量急剧增加。此时,B220(+)细胞表达表面(s)IgM,但几乎所有B220(LOW) CD138(+)细胞同时显示细胞内(i)IgM和IgG2a。滤泡性和边缘区B细胞均被激活,表达大量CD69。感染后第40天,B220(LOW) CD138(+)细胞群体仍然增加,但与急性感染不同的是,这些细胞中有61.1%的细胞iIgG2a呈阳性,而只有14.2%的细胞表达iIgM。此外,在感染后第20天和第40天,分别有29.2%和13.0%的B220(+)细胞表达sIgG2a。根据细胞大小以及CD80、CD86、CD11b、CD44和CD38的表达情况,B220(+) sIgG2a(+)细胞具有活化/记忆B细胞的表型特征。此外,感染后第30天,14.1%的B220(+) sIgG2a(+)细胞表达边缘区B细胞表型。重要的是,来自感染40天小鼠的B细胞在呈递寄生虫抗原方面非常有效,可导致CD4(+)和CD8(+)细胞增殖。我们的结果有助于理解恰氏疟原虫感染期间B细胞的动态变化,揭示抗原呈递和抗体产生的机制,这些对于获得针对疟疾的保护性免疫至关重要。

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