Rotavirus Differentially Infects and Polyclonally Stimulates Human B Cells Depending on Their Differentiation State and Tissue of Origin
Rotavirus Differentially Infects and Polyclonally Stimulates Human B Cells Depending on Their Differentiation State and Tissue of Origin
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DOI：
10.1128/jvi.02550-09
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发表时间：
2010-05-01
影响因子：
5.4
通讯作者：
Greenberg, Harry B.
中科院分区：
文献类型：
--
作者：
Narvaez, Carlos F.;Franco, Manuel A.;Greenberg, Harry B.
我们以前已经证明轮状病毒（RV）可以感染小鼠肠道B220（+）细胞（M。Fenaux，M. A. Cuadras，N.冯，M. Jaimes和H. B。Greenberg，J. Virol. 80：5219-5232，2006）和体外人血B细胞（M. C.梅萨湖S.罗德里格斯，M。A. Franco和J. Angel，Virology 366：174-184，2007）。然而，RV对B细胞的影响，特别是那些存在于人肠道，RV感染的主要部位，是未知的。在这里，我们比较了RV体外感染人循环（CBC）和肠B细胞（IBC）的影响。RV感染的IBC是CBC的四倍，在两种类型的B细胞中，病毒复制高度限于记忆亚群。RV分别在30%和3%感染的CBC和IBC中诱导细胞死亡。此外，当B细胞与其他单核细胞共存时，RV诱导CBC的抗体分泌细胞（ASC）活化和分化，但不诱导IBC的抗体分泌细胞（ASC）活化和分化。然而，RV在纯化的CBC或IBC中不诱导这些效应，表明其他细胞参与激活和分化CBC。RV感染与CBC测定的白细胞介素-6（IL-6）产生增强相关，而与病毒复制无关。抗B细胞受体、脂多糖或CpG刺激的CBC的感染减少了IL-6和IL-8的分泌，并减少了ASC的数量。这些抑制作用与病毒复制和细胞死亡的增加有关，在多克隆刺激的CBC中观察到，但在IBC中没有观察到。因此，RV与原代人B细胞的相互作用取决于它们的来源组织和分化阶段，并且它影响它们调节局部和全身免疫应答的能力。
We have shown previously that rotavirus (RV) can infect murine intestinal B220(+) cells in vivo (M. Fenaux, M. A. Cuadras, N. Feng, M. Jaimes, and H. B. Greenberg, J. Virol. 80: 5219-5232, 2006) and human blood B cells in vitro (M. C. Mesa, L. S. Rodriguez, M. A. Franco, and J. Angel, Virology 366: 174-184, 2007). However, the effect of RV on B cells, especially those present in the human intestine, the primary site of RV infection, is unknown. Here, we compared the effects of the in vitro RV infection of human circulating (CBC) and intestinal B cells (IBC). RV infected four times more IBC than CBC, and in both types of B cells the viral replication was highly restricted to the memory subset. RV induced cell death in 30 and 3% of infected CBC and IBC, respectively. Moreover, RV induced activation and differentiation into antibody-secreting cells (ASC) of CBC but not IBC when the B cells were present with other mononuclear cells. However, RV did not induce these effects in purified CBC or IBC, suggesting the participation of other cells in activating and differentiating CBC. RV infection was associated with enhanced interleukin-6 (IL-6) production by CBC independent of viral replication. The infection of the anti-B-cell receptor, lipopolysaccharide, or CpG-stimulated CBC reduced the secretion of IL-6 and IL-8 and decreased the number of ASC. These inhibitory effects were associated with an increase in viral replication and cell death and were observed in polyclonally stimulated CBC but not in IBC. Thus, RV differentially interacts with primary human B cells depending on their tissue of origin and differentiation stage, and it affects their capacity to modulate the local and systemic immune responses.