HIV-1 感染中的 B 细胞异常：IgG3 和 T-bet 的作用。
B-cell abnormalities in HIV-1 infection: roles for IgG3 and T-bet.
机构信息
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
出版信息
Curr Opin HIV AIDS. 2019 Jul;14(4):240-245. doi: 10.1097/COH.0000000000000547.
PURPOSE OF REVIEW
Numerous B-cell abnormalities in HIV-1 infection have been described over the past three decades yet have remained poorly defined mechanistically. We review recent studies that describe mechanisms of B-cell dysregulation in chronic HIV-1 infection associated with IgG3 and T-bet.
RECENT FINDINGS
HIV-1 infection causes hypergammaglobulinemia and dysregulation of B-cell populations, including the expansion during chronic viremia of functionally impaired tissue-like memory (TLM) B cells. TLM B cells and B cells in other conditions of chronic activation and inflammation with similar phenotypes are characterized by increased expression of the transcription factor T-bet and preferential immunoglobulin class-switching to IgG3. However, defects in B-cell function during chronic HIV-1 viremia are also associated with the binding of soluble IgG3 to IgM-expressing B cells, with the highest intensities observed on TLM B cells. The consequence of IgG3 binding to TLM B cells is increased clustering of the IgM B-cell receptor and decreased response to stimulation.
SUMMARY
The identification of T-bet and IgG3 as the regulators of B-cell function in chronic HIV-1 viremia could provide new targets for therapeutic intervention aimed at reversing the damaging effects of HIV-1-associated chronic immune activation.
目的综述
在过去的三十年中，人们已经描述了 HIV-1 感染中大量的 B 细胞异常，但这些异常在机制上仍未得到很好的定义。我们回顾了最近的研究，这些研究描述了与 IgG3 和 T-bet 相关的慢性 HIV-1 感染中 B 细胞失调的机制。
最近的发现
HIV-1 感染会导致高丙种球蛋白血症和 B 细胞群体失调，包括在慢性病毒血症期间功能受损的组织样记忆 (TLM) B 细胞的扩增。TLM B 细胞和其他处于慢性激活和炎症状态的具有相似表型的 B 细胞的特征是转录因子 T-bet 的表达增加，并且优先免疫球蛋白类别转换为 IgG3。然而，慢性 HIV-1 病毒血症期间 B 细胞功能的缺陷也与可溶性 IgG3 与表达 IgM 的 B 细胞结合有关，在 TLM B 细胞上观察到最高的结合强度。IgG3 与 TLM B 细胞结合的后果是 IgM B 细胞受体的聚集增加和对刺激的反应性降低。
总结
将 T-bet 和 IgG3 鉴定为慢性 HIV-1 病毒血症中 B 细胞功能的调节剂，可以为旨在逆转 HIV-1 相关慢性免疫激活的破坏性影响的治疗干预提供新的靶点。
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