B-1 B cells as a source of polyreactive IgE antibodies, in allergic individuals

过敏性疾病是由称为B细胞的细胞产生的抗体分子的作用引起的。在过去的15年里，人们已经意识到至少有两个B细胞亚群，称为B-1和B-2细胞。B-1细胞及其抗体产物具有许多不寻常的特征，它们与一些疾病过程有关。我们最近完成的研究有力地表明，B-1B细胞可能在一些过敏性疾病中发挥重要作用。我们希望比较根据他们的过敏条件和年龄定义的患者组，看看B-1B细胞活动是否与特定的过敏性疾病有关。我们假设，患有过敏性皮肤疾病的患者增加了诱发过敏的B-1细胞的数量。这些患者将与对吸入性过敏原过敏的患者和其他对食物过敏的患者进行比较。研究将在成人群体中进行，也将在儿童中进行，因为众所周知，B-1B细胞的数量随年龄而变化。在过敏性疾病的背景下，我们对B细胞功能调节的大部分了解都来自于对传统B-2细胞进行的研究，我们也希望重新考虑B细胞调节的一些方面。我们特别感兴趣的是，当B-1B细胞从产生非过敏型抗体(IgM抗体)转变为促进过敏的IgE抗体时，B-1B细胞“转换”的调节。我们希望确定当受到称为细胞因子的调节分子的影响时，过敏个体的B-1B细胞是否特别容易受到这种转换的影响。我们预计B-1B细胞将与一些尽管不是所有的过敏性疾病有关，这些细胞将成为治疗的新靶点。这样的发现将是最重要的。新疗法的开发将需要更好地了解这些细胞的调节，这将是该项目的另一个重要成果。

Allergic disease results from the actions of antibody molecules that are produced by cells called B cells. Over the last fifteen years, it has been realised that there are at least two B cell subsets, called B-1 and B-2 cells. The B-1 cells and their antibody products have many unusual features, and they have been implicated in some disease processes. We have recently completed studies that strongly suggest that B-1 B cells may play an important role in some allergic disease. We wish to compare groups of patients defined according to their allergic conditions and age, to see whether B-1 B cell activity is associated with particular allergic diseases. We hypothesise that patients with allergic skin conditions have raised numbers of allergy-inducing B-1 cells. Such patients will be compared with those with allergies to inhalent allergens and others with food allergies. Studies will be performed in adult groups as well as in children, for B-1 B cell numbers are known to vary with age. As most of our understanding of the regulation of B cell function, in the context of allergic disease, has arisen from studies conducted with conventional B-2 cells, we also wish to reconsider aspects of B cell regulation. We are specifically interested in the regulation of the 'switching' of B-1 B cells, when they change from the production of antibodies of a 'non-allergic' type (IgM antibodies) to allergy-promoting IgE antibodies. We wish to determine whether the B-1 B cells of allergic individuals are particularly susceptible to such switching, when under the influence of regulatory molecules called cytokines. We expect that B-1 B cells will be associated with some, though not all allergic conditions, and that these cells will emerge as a new target for therapies. Such a finding would be most important. The development of new therapies will require a better understanding of the regulation of these cells, and this will be another important outcome of this project.