Genestier Laurent, Taillardet Morgan, Mondiere Paul, Gheit Hanane, Bella Chantal, Defrance Thierry
Institut National de la Santé et de la Recherche Médicale Unité 851, IFR128 Biosciences Lyon-Gerland, 21 Avenue Tony Garnier, Lyon, France.
J Immunol. 2007 Jun 15;178(12):7779-86. doi: 10.4049/jimmunol.178.12.7779.
Naive murine B cells are known to proliferate and differentiate in response to LPS or CpG, which bind to TLR4 and TLR9, respectively. However, the naive murine B cell compartment is heterogeneous and comprises four different B cell subsets: B-1a, B-1b, marginal zone (MZ), and follicular (FO) B cells. B-1a, B-1b, and MZ B cells are specialized in the response to thymus-independent Ag, and FO B cells are involved in the response to thymus-dependent Ag. This study was undertaken to compare those four naive B cell subsets for their responses to TLR agonists. Quantitative RT-PCR analysis revealed that expression of TLR transcripts differs quantitatively but not qualitatively from one subset to the other. All TLR agonists, with the exception of flagellin and poly(I:C), stimulate B cell proliferation whatever the subset considered. However, TLR ligation leads to massive differentiation of B-1 and MZ B cells into mature plasma cells (PC) but only marginally promotes PC differentiation of FO B cells. Moreover, TLR stimulation strongly up-regulates expression of Blimp-1 and XBP-1(S), two transcription factors known to be instrumental in PC differentiation, in B-1 and MZ B cells but not in FO B cells. Altogether, our findings suggest that B-1 and MZ B cells are poised to PC differentiation in response to the microbial environment and that TLR agonists can be instrumental in stimulating Ab-mediated innate immune protection during microbial infections.
已知未成熟的小鼠B细胞会因分别与Toll样受体4（TLR4）和Toll样受体9（TLR9）结合的脂多糖（LPS）或CpG而增殖和分化。然而，未成熟的小鼠B细胞区室是异质性的，由四种不同的B细胞亚群组成：B-1a、B-1b、边缘区（MZ）和滤泡（FO）B细胞。B-1a、B-1b和MZ B细胞专门针对非胸腺依赖性抗原作出反应，而FO B细胞则参与对胸腺依赖性抗原的反应。本研究旨在比较这四种未成熟B细胞亚群对TLR激动剂的反应。定量逆转录聚合酶链反应（RT-PCR）分析显示，TLR转录本的表达在不同亚群之间存在数量差异，但无质量差异。除鞭毛蛋白和聚肌苷酸-聚胞苷酸（poly(I:C)）外，所有TLR激动剂无论所考虑的亚群如何，均能刺激B细胞增殖。然而，TLR连接导致B-1和MZ B细胞大量分化为成熟浆细胞（PC），但仅轻微促进FO B细胞的PC分化。此外，TLR刺激在B-1和MZ B细胞中强烈上调Blimp-1和XBP-1(S)的表达，这两种转录因子已知在PC分化中起重要作用，但在FO B细胞中则不然。总之，我们的研究结果表明，B-1和MZ B细胞准备好在微生物环境中分化为PC，并且TLR激动剂在微生物感染期间刺激抗体介导的先天性免疫保护中可能起重要作用。
