Induction of bronchus-associated lymphoid tissue is an early life adaptation for promoting human B cell immunity.
Induction of bronchus-associated lymphoid tissue is an early life adaptation for promoting human B cell immunity.
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支气管相关淋巴组织的诱导是促进人类 B 细胞免疫的早期生命适应。
DOI：
10.1038/s41590-023-01557-3
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发表时间：
2023
影响因子：
30.5
通讯作者：
中科院分区：
文献类型：
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作者：
Matsumoto,Rei;Gray,Joshua;Rybkina,Ksenia;Oppenheimer,Hanna;Levy,Lior;Friedman,LilachM;Khamaisi,Muhammad;Meng,Wenzhao;Rosenfeld,AaronM;Guyer,RebeccaS;Bradley,MarissaC;Chen,David;Atkinson,MarkA;Brusko,ToddM;Brusko,Maigan;
婴幼儿比成人更容易受到常见呼吸道病原体的影响，但对严重急性呼吸综合征冠状病毒 2 等新型病原体的抵抗力更好。婴幼儿对呼吸道病原体产生有效免疫反应的机制尚不清楚。通过对 0-13 岁婴儿和儿科器官捐献者的肺部和肺相关淋巴结的研究，我们发现支气管相关淋巴组织 (BALT) 在婴儿期发育，其中含有 B 细胞滤泡、CD4+T 细胞和功能活跃的生发中心。 BALT 结构在生命的前 3 年普遍存在于肺气道周围，其数量在儿童时期随着记忆 T 细胞的积累而下降。单细胞分析和谱分析表明，早期肺 B 细胞经历分化、体细胞超突变和免疫球蛋白类别转换，并表现出比淋巴结 B 细胞更活跃的特征。此外，与循环抗体相比，肺和肺相关淋巴结中的 B 细胞对多种呼吸道病原体产生有偏向的抗体反应，循环抗体大多对生命早期的疫苗抗原具有特异性。总之，我们的研究结果为 BALT 作为一种早期生命适应提供了证据，可以在这个生命形成阶段动员局部免疫保护来应对各种呼吸挑战。
Infants and young children are more susceptible to common respiratory pathogens than adults but can fare better against novel pathogens like severe acute respiratory syndrome coronavirus 2. The mechanisms by which infants and young children mount effective immune responses to respiratory pathogens are unknown. Through investigation of lungs and lung-associated lymph nodes from infant and pediatric organ donors aged 0–13 years, we show that bronchus-associated lymphoid tissue (BALT), containing B cell follicles, CD4+T cells and functionally active germinal centers, develop during infancy. BALT structures are prevalent around lung airways during the first 3 years of life, and their numbers decline through childhood coincident with the accumulation of memory T cells. Single-cell profiling and repertoire analysis reveals that early life lung B cells undergo differentiation, somatic hypermutation and immunoglobulin class switching and exhibit a more activated profile than lymph node B cells. Moreover, B cells in the lung and lung-associated lymph nodes generate biased antibody responses to multiple respiratory pathogens compared to circulating antibodies, which are mostly specific for vaccine antigens in the early years of life. Together, our findings provide evidence for BALT as an early life adaptation for mobilizing localized immune protection to the diverse respiratory challenges during this formative life stage.