Background

Type 3 innate lymphoid cells (ILC3s) are involved in maintenance of mucosal homeostasis; however, their role in immunoregulation has been unknown. Immature transitional regulatory B (itBreg) cells are innate-like B cells with immunosuppressive properties, and the in vivo mechanisms by which they are induced have not been fully clarified.

Objective

We aimed to investigate the ILC3–B-cell interaction that probably takes place in human tonsils.

Methods

ILC3s were isolated from peripheral blood and palatine tonsils, expanded, and cocultured with naive B cells. Tonsillar ILC3s and regulatory B cells were visualized with immunofluorescence histology. ILC3 frequencies were measured in tonsil tissue of allergic and nonallergic patients and in peripheral blood of allergic asthmatic patients and healthy control subjects.

Results

A mutually beneficial relationship was revealed between ILC3s and B cells: ILC3s induced IL-15 production in B cells through B cell–activating factor receptor, whereas IL-15, a potent growth factor for ILC3s, induced CD40 ligand (CD40L) expression on circulating and tonsillar ILC3s. IL-15–activated CD40L⁺ ILC3s helped B-cell survival, proliferation, and differentiation of IL-10–secreting, PD-L1–expressing functional itBreg cells in a CD40L- and B cell–activating factor receptor–dependent manner. ILC3s and regulatory B cells were in close connection with each other in palatine tonsils. ILC3 frequency was reduced in tonsil tissue of allergic patients and in peripheral blood of allergic asthmatic patients.

Conclusion

Human CD40L⁺ ILC3s provide innate B-cell help and are involved in an innate immunoregulatory mechanism through induction of itBreg cell differentiation, which takes place in palatine tonsils in vivo. This mechanism, which can contribute to maintenance of immune tolerance, becomes insufficient in allergic diseases.

中文翻译：

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表达人类CD40配体的3型先天淋巴样细胞诱导产生IL-10的未成熟过渡调节性B细胞

背景

3型先天淋巴样细胞（ILC3）参与维持粘膜稳态。然而，它们在免疫调节中的作用尚不清楚。未成熟的过渡调节性B（itBreg）细胞是具有免疫抑制特性的先天性B细胞，诱导它们的体内机制尚未完全阐明。

客观的

我们旨在研究可能在人类扁桃体中发生的ILC3-B细胞相互作用。

方法

从外周血和p扁桃体中分离出ILC3，进行扩增，并与幼稚B细胞共培养。扁桃体ILC3和调节性B细胞通过免疫荧光组织学观察。在变应性和非变应性患者的扁桃体组织以及变应性哮喘患者和健康对照组的外周血中测量ILC3频率。

结果

ILC3s与B细胞之间揭示了一种互利的关系：ILC3s通过B细胞激活因子受体诱导B细胞中IL-15的产生，而IL-15s的潜在生长因子IL-15诱导循环中CD40配体（CD40L）的表达。和扁桃体ILC3。IL-15激活的CD40L ⁺ ILC3s以依赖CD40L和B细胞的激活因子受体的方式帮助了分泌IL-10的，表达PD-L1的功能性itBreg细胞的B细胞存活，增殖和分化。ILC3和调节性B细胞在3扁桃体中彼此紧密相连。变应性患者的扁桃体组织和变应性哮喘患者的外周血中ILC3频率降低。

结论

人CD40L ⁺ ILC3提供先天B细胞帮助，并通过诱导itBreg细胞分化而参与先天免疫调节机制，这种分化发生在体内vivo扁桃体中。在过敏性疾病中，这种有助于维持免疫耐受性的机制变得不足。