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Assembly of a spatial circuit of T-bet–expressing T and B lymphocytes is required for antiviral humoral immunity
Science Immunology ( IF 24.8 ) Pub Date : 2021-06-11 , DOI: 10.1126/sciimmunol.abi4710
Alejandra Mendoza 1 , William T Yewdell 2 , Beatrice Hoyos 1 , Michail Schizas 1 , Regina Bou-Puerto 1, 3 , Anthony J Michaels 1, 3 , Chrysothemis C Brown 1 , Jayanta Chaudhuri 2, 3, 4 , Alexander Y Rudensky 1, 3
Affiliation  

Effective antiviral immunity requires generation of T and B lymphocytes expressing the transcription factor T-bet, a regulator of type 1 inflammatory responses. Using T-bet expression as an endogenous marker for cells participating in a type 1 response, we report coordinated interactions of T-bet–expressing T and B lymphocytes on the basis of their dynamic colocalization at the T cell zone and B follicle boundary (T-B boundary) and germinal centers (GCs) during lung influenza infection. We demonstrate that the assembly of this circuit takes place in distinct anatomical niches within the draining lymph node, guided by CXCR3 that enables positioning of TH1 cells at the T-B boundary. The encounter of B and TH1 cells at the T-B boundary enables IFN-γ produced by the latter to induce IgG2c class switching. Within GCs, T-bet+ TFH cells represent a specialized stable sublineage required for GC growth but dispensable for IgG2c class switching. Our studies show that during respiratory viral infection, T-bet–expressing T and B lymphocytes form a circuit assembled in a spatiotemporally controlled manner that acts as a functional unit enabling a robust and coherent humoral response tailored for optimal antiviral immunity.



中文翻译:

抗病毒体液免疫需要组装表达 T-bet 的 T 和 B 淋巴细胞的空间回路

有效的抗病毒免疫需要产生表达转录因子 T-bet 的 T 和 B 淋巴细胞,T-bet 是 1 型炎症反应的调节因子。使用 T-bet 表达作为参与 1 型反应的细胞的内源性标记,我们报告了表达 T-bet 的 T 和 B 淋巴细胞的协调相互作用,基于它们在 T 细胞区和 B 卵泡边界 (TB) 的动态共定位边界)和生发中心(GCs)在肺流感感染期间。我们证明该回路的组装发生在引流淋巴结内不同的解剖壁龛中,由 CXCR3 引导,能够将 T H 1 细胞定位在 TB 边界。B和T H的相遇TB 边界处的 1 细胞使后者产生的 IFN-γ 能够诱导 IgG2c 类别转换。在 GC 中,T-bet + T FH细胞代表了 GC 生长所需的专门稳定的亚系,但对于 IgG2c 类别转换是可有可无的。我们的研究表明,在呼吸道病毒感染期间,表达 T-bet 的 T 淋巴细胞和 B 淋巴细胞形成一个以时空控制方式组装的回路,作为一个功能单元,能够产生针对最佳抗病毒免疫的稳健而连贯的体液反应。

更新日期:2021-06-13
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