Background

The importance of B lymphocytes to present antigens for antibody production is well documented. In contrast, very little is known about their capacity to influence CD4⁺ T-cell activation during a primary or secondary response to allergens.

Objective

Using mouse models of asthma, we investigated the role of B cells as antigen-presenting cells in priming and maintenance of T_H cell responses.

Methods

Mice were immunized through the intranasal route with house dust mite (HDM) extract derived from Dermatophagoides pteronyssinus. B cells were depleted in HDM-sensitized animals to investigate the importance of B cells in maintenance of the allergic response. B cells were depleted before HDM sensitization to investigate the role of B cells in T-cell priming; furthermore, HDM sensitization was performed in mice with MHC class II expression restricted to the B-cell lineage.

Results

We found that B cells serve as potent antigen-presenting cells ex vivo and restimulate in vivo–primed HDM-specific T_H cells. HDM antigens were taken up by B cells independently of B-cell receptor specificity, indicating that HDM uptake and antigen presentation to CD4⁺ T cells is not restricted to rare B cells carrying HDM-specific B cell receptors. B-cell depletion before HDM challenge in HDM-sensitized mice resulted in a dramatic reduction of allergic response, indicating the role of B cells in amplification of T_H2 responses. In contrast, HDM sensitization of mice in which MHC class II expression was restricted to B cells revealed the inability of these cells to prime T_H2 responses but highlighted their unexpected role in priming T_H1 and T_H17 responses.

Conclusion

Collectively, these data reveal new mechanisms leading to initiation and exacerbation of the allergic response that might have implications for designing new therapeutic strategies to combat HDM allergy.

中文翻译：

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在哮喘小鼠模型中，B细胞在T _H细胞反应中的作用

背景

B淋巴细胞呈递抗原以生产抗体的重要性已得到充分证明。相反，人们对它们在对过敏原的主要或次要反应过程中影响CD4 ⁺ T细胞活化的能力知之甚少。

客观的

使用哮喘小鼠模型，我们调查了B细胞作为抗原呈递细胞在引发和维持T _H细胞反应中的作用。

方法

通过鼻内途径用衍生自Dermatophagoides pteronyssinus的屋尘螨（HDM）提取物对小鼠进行免疫。B细胞在HDM致敏动物中耗竭，以研究B细胞在维持过敏反应中的重要性。在HDM致敏之前耗尽B细胞，以研究B细胞在T细胞启动中的作用；此外，在MHC II类表达受限于B细胞谱系的小鼠中进行了HDM致敏。

结果

我们发现B细胞可作为离体的有效抗原呈递细胞，并在体内重新激活初次启动的HDM特异T _H细胞。B细胞不依赖B细胞受体特异性而吸收HDM抗原，这表明HDM摄取和抗原呈递给CD4 ⁺ T细胞并不限于携带HDM特异性B细胞受体的罕见B细胞。在HDM致敏的小鼠中，在HDM攻击前B细胞耗竭导致过敏反应显着降低，表明B细胞在T _H 2反应放大中的作用。相比之下，其中MHC II类表达仅限于B细胞的小鼠的HDM致敏反应表明，这些细胞无法引发T _H2个应答，但突出了它们在引发T _H 1和T _H 17应答中的意外作用。

结论

总的来说，这些数据揭示了导致引发和加剧过敏反应的新机制，这可能对设计新的对抗HDM过敏的治疗策略有影响。