Molnarfi Nicolas, Bjarnadóttir Kristbjörg, Benkhoucha Mahdia, Juillard Catherine, Lalive Patrice H
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Unit of Neuroimmunology and Multiple Sclerosis, Division of Neurology, Department of Clinical Neurosciences, Geneva University Hospital, Geneva, Switzerland.
J Neuroinflammation. 2017 Jan 19;14(1):13. doi: 10.1186/s12974-017-0798-5.
Accumulating evidence indicate that B cells can exhibit pro- or anti-inflammatory activities. Similar to interleukin (IL)-10-competent B cells, we recently showed that transforming growth factor (TGF)-β1-producing regulatory B cells limit the induction of autoimmune neuroinflammation in mice, making them potentially important in maintaining peripheral immune tolerance in central nervous system inflammatory demyelinating disorders such as multiple sclerosis.
In this study, we compared B cell production of TGF-β1 and IL-10, the two most studied regulatory cytokines, and the pro-inflammatory B cell-derived IL-6 and tumor necrosis factor cytokines under basal conditions and following polyclonal stimulation with dual B cell receptor (BCR) cross-linking and Toll-like receptor (TLR)9 engagement.
We showed that resting TGF-β1-producing B cells fall within both the naïve (CD27) and memory (CD27) B cell compartments. We found no spontaneous B cell-derived IL-10, IL-6 or tumor necrosis factor (TNF) production. Human B cell activation with anti-Ig antibodies plus CPG-B leads to only modest IL-10 production by memory CD19CD27 B cells while expression levels of IL-6 and TNF by both naive and memory B cells were strongly induced. Remarkably, stimulated B cells showed significantly reduced capacity to produce TGF-β1.
These findings indicate that B cell activation may facilitate the development of excessive immune responses and autoimmunity by restricting B cell-derived TGF-β1 production by resting B cells and favoring in turns the proinflammatory actions of activated cytokine-producing B cells.
越来越多的证据表明B细胞可表现出促炎或抗炎活性。与具有白细胞介素（IL）-10功能的B细胞类似，我们最近发现，产生转化生长因子（TGF）-β1的调节性B细胞可限制小鼠自身免疫性神经炎症的诱导，这使其在维持中枢神经系统炎性脱髓鞘疾病（如多发性硬化症）的外周免疫耐受中可能具有重要作用。
在本研究中，我们比较了在基础条件下以及用双B细胞受体（BCR）交联和Toll样受体（TLR）9激活进行多克隆刺激后，B细胞产生的TGF-β1和IL-10这两种研究最多的调节性细胞因子，以及促炎性B细胞衍生的IL-6和肿瘤坏死因子细胞因子。
我们发现，静息状态下产生TGF-β1的B细胞存在于初始（CD27⁻）和记忆（CD27⁺）B细胞亚群中。我们未发现B细胞自发产生IL-10、IL-6或肿瘤坏死因子（TNF）。用抗Ig抗体加CPG-B激活人B细胞，仅使记忆性CD19⁺CD27⁺ B细胞产生适度的IL-10，而初始和记忆B细胞的IL-6和TNF表达水平均被强烈诱导。值得注意的是，受刺激的B细胞产生TGF-β1的能力显著降低。
这些发现表明，B细胞激活可能通过限制静息B细胞产生B细胞衍生的TGF-β1，并转而有利于激活的产生细胞因子的B细胞的促炎作用，从而促进过度免疫反应和自身免疫的发展。
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