Trypanosoma cruzi infection induces a massive extrafollicular and follicular splenic B-cell response which is a high source of non-parasite-specific antibodies
Trypanosoma cruzi infection induces a massive extrafollicular and follicular splenic B-cell response which is a high source of non-parasite-specific antibodies
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DOI：
10.1111/j.1365-2567.2010.03347.x
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发表时间：
2011-01-01
期刊：
影响因子：
6.4
通讯作者：
Gruppi, Adriana
中科院分区：
文献类型：
--
作者：
Bermejo, Daniela A.;Amezcua Vesely, Maria C.;Gruppi, Adriana
克氏锥虫是南美锥虫病的病原体，急性感染可导致寄生虫血症和多克隆淋巴细胞活化。据报道，多克隆B细胞活化与高丙种球蛋白血症和延迟的寄生虫特异性抗体反应有关。在本研究中，我们分析了急性T淋巴细胞白血病时脾脏不同微环境中B细胞反应的发展。克氏感染我们观察到大量的生发中心（GC）和卵泡外（EF）的反应，在感染的高峰期。然而，从感染后（p.i.）第3天开始，EF病灶明显，在感染早期，它们主要提供IgM。EF病灶反应在感染后11天达到峰值。并从红髓延伸到动脉周围淋巴鞘。从感染后第8天检测GC。在寄生虫血症高峰期，EF病灶、红髓和T细胞带中的CD 138 + B220+浆细胞表达IgM和所有IgG同种型。脾细胞产生的大多数抗体并不靶向寄生虫，而不是大量的B细胞应答，只有在感染后18天才能在血清中检测到寄生虫特异性IgG同种型。我们还观察到，与正常小鼠相比，感染小鼠的骨髓中CD 138 + B220+细胞显著减少。因此，在急性感染T. cruzi，脾似乎是最重要的淋巴器官，其存放浆细胞和抗体的主要产生者。在T. cruzi感染表现出T. cruzi和其它原生动物感染，但不同于其它感染或用模型抗原免疫。
P>Acute infection with Trypanosoma cruzi, the aetiological agent of Chagas' disease, results in parasitaemia and polyclonal lymphocyte activation. It has been reported that polyclonal B-cell activation is associated with hypergammaglobulinaemia and delayed parasite-specific antibody response. In the present study we analysed the development of a B-cell response within the different microenvironments of the spleen during acute T. cruzi infection. We observed massive germinal centre (GC) and extrafollicular (EF) responses at the peak of infection. However, the EF foci were evident since day 3 post-infection (p.i.), and, early in the infection, they mainly provided IgM. The EF foci response reached its peak at 11 days p.i. and extended from the red pulp into the periarteriolar lymphatic sheath. The GCs were detected from day 8 p.i. At the peak of parasitaemia, CD138+ B220+ plasma cells in EF foci, red pulp and T-cell zone expressed IgM and all the IgG isotypes. Instead of the substantial B-cell response, most of the antibodies produced by splenic cells did not target the parasite, and parasite-specific IgG isotypes could be detected in sera only after 18 days p.i. We also observed that the bone marrow of infected mice presented a strong reduction in CD138+ B220+ cells compared with that of normal mice. Hence, in acute infection with T. cruzi, the spleen appears to be the most important lymphoid organ that lodges plasma cells and the main producer of antibodies. The development of a B-cell response during T. cruzi infection shows features that are particular to T. cruzi and other protozoan infection but different to other infections or immunization with model antigens.