PDF(Pubmed)
Abstract：
Insights into the immunopathogenesis of chronic HBV infections are fundamental in the quest for novel treatment approaches aimed at a functional cure. While much is known about the ineffective HBV-specific T-cell responses that characterise persistent HBV replication, B cells have been left largely understudied. However, an important role for humoral immunity during the natural history of HBV infections, as well as after functional cure, has been inadvertently revealed by the occurrence of HBV flares following B cell-depleting treatments. Herein, we review our current understanding of the role of the humoral immune response in chronic HBV, both at the level of HBV-specific antibody production and at the phenotypic and broader functional level of B cells. The recent development of fluorescently labelled HBV proteins has given us unprecedented insights into the phenotype and function of HBsAg- and HBcAg-specific B cells. This should fuel novel research into the mechanisms behind dysfunctional HBsAg-specific and fluctuating, possibly pathogenic, HBcAg-specific B-cell responses in chronic HBV. Finally, novel immunomodulatory treatments that partly target B cells are currently in clinical development, but a detailed assessment of their impact on HBV-specific B-cell responses is lacking. We plead for a rehabilitation of B-cell studies related to both the natural history of HBV and treatment development programmes.
摘要：
对慢性HBV感染的免疫发病机制的见解是寻求旨在功能性治愈的新型治疗方法的基础。虽然很多是已知的无效的HBV特异性T细胞反应，表征持续HBV复制，B细胞已被大量研究。然而,在HBV感染的自然史体液免疫的重要作用，以及功能治愈后，B细胞消耗治疗后HBV耀斑的发生无意中揭示了。在这里，我们回顾了我们目前对慢性HBV的体液免疫反应的作用的理解，在HBV特异性抗体产生水平和B细胞的表型和更广泛的功能水平。荧光标记的HBV蛋白的最新发展使我们对HBsAg和HBcAg特异性B细胞的表型和功能具有前所未有的认识。这应该燃料新的研究到功能失调的HBsAg特异性和波动背后的机制，可能是致病的,慢性HBV中的HBcAg特异性B细胞反应。最后,部分靶向B细胞的新型免疫调节治疗目前正在临床开发中，但缺乏对HBV特异性B细胞反应的影响的详细评估。我们恳求与HBV的自然史和治疗开发计划相关的B细胞研究的康复。
