Tolerance and Intolerance Characteristics of IgG B-Cell Receptor Immune Repertoires in Children with Chronic Hepatitis B Infections. Homo sapiens

Children with chronic hepatitis B infections pose serious medical challenges because they eventually become disease-seeding adults and suffer from complications for life. Vaccination is the best method to prevent the illness but is ineffective in children carriers. This study uses in-depth analyses of IgG B-cell receptor immune repertoires among carrier and noncarrier siblings to comprehensively characterize infection statuses and vaccine responses. A huge set of sequence-related clones of complementarity determining region 3 (CDR3) on IgG heavy chains indeed presents exclusively among carriers, marking the struggling immune intolerance against the persistent infections. Vaccination on the contrary brings about significant increases of CDR3 diversities in noncarriers but not in carriers who have instead tolerated the vaccine antigen. Clone clusters associated with the immune reactions in noncarriers are identified accordingly. In sum both tolerance and intolerance aspects of IgG immune repertoires have been revealed at resolutions unprecedented ever for children with chronic hepatitis B infections.

慢性乙型肝炎（chronic hepatitis B）感染患儿面临严峻的临床挑战：此类患儿终将成长为病毒传染源成年患者，并终身饱受并发症的困扰。疫苗接种是预防该疾病的最优手段，但对慢性乙肝病毒携带儿童却无效。本研究通过对携带与非携带乙肝病毒的同胞群体开展免疫球蛋白G（IgG）B细胞受体（B-cell receptor）免疫组库的深度分析，全面刻画了感染状态与疫苗应答特征。研究发现，大量与IgG重链上互补决定区3（CDR3）序列相关的克隆仅特异性存在于病毒携带者群体中，这标志着机体针对持续性感染陷入了难以突破的免疫耐受困境。与之相反，疫苗接种可使非携带者的CDR3序列多样性显著提升，但对携带者却无此效果——此时携带者已对疫苗抗原产生了免疫耐受。研究据此成功鉴定出与非携带者免疫反应相关的克隆簇。综上，本研究以前所未有的分辨率，首次揭示了慢性乙型肝炎感染患儿IgG免疫组库的免疫耐受与免疫不耐受双重特征。