Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Shuangyong Road 6, Nanning, Guangxi Zhuang Autonomous Region 530021, Peoples Republic of China.
Coronary Care Unit, Nanning First People"s Hospital. Qixing Road 89, Nanning, Guangxi Zhuang Autonomous Region 530021, Peoples Republic of China.
Clin Exp Immunol. 2022 May 13;208(1):1-11. doi: 10.1093/cei/uxac015.
Although B cells are essential for humoral immunity and show noteworthy immunomodulatory activity through antibody-independent functions, the role of B cells in regulating Treg cell responses remains controversial. Tregs (CD4+CD25+Foxp3+) are considered to play an immunoprotective role in viral myocarditis (VMC) by controlling autoimmune effector T cells. Here, we proved that B-cell knockout can not only lead to significant reductions in Tregs in the spleen, blood, and heart of VMC mice but also decrease the activation and immune function of splenic Tregs, which was reversed by adoptive transfer of B cells; the transcription levels of TGF-β and Foxp3 in the myocardium were also significantly reduced. B-cell depletion by anti-CD20 impaired the anti-inflammatory function of splenic Tregs and the homeostasis of myocardial Tregs population. Moreover, B cells can convert CD4+CD25- T cells into Foxp3+ and Foxp3-, two functionally suppressive Treg subgroups. Although the reduction in myocardial inflammation in BKO mice indicates that B cells may play a proinflammatory role, the beneficial side of B cells cannot be ignored, that is, to control autoimmunity by maintaining Treg numbers. The results observed in the animal model of VMC highlight the potential harm of rituximab in the nonselective depletion of B cells in clinical applications.
虽然 B 细胞对于体液免疫是必需的，并且通过非抗体依赖的功能表现出显著的免疫调节活性，但 B 细胞在调节 Treg 细胞反应中的作用仍存在争议。Tregs（CD4+CD25+Foxp3+）被认为通过控制自身免疫效应 T 细胞在病毒性心肌炎（VMC）中发挥免疫保护作用。在这里，我们证明 B 细胞敲除不仅可以导致 VMC 小鼠脾脏、血液和心脏中的 Tregs 显著减少，还可以降低脾 Tregs 的活化和免疫功能，而通过 B 细胞的过继转移可以逆转这种情况；心肌中的 TGF-β和 Foxp3 的转录水平也显著降低。抗 CD20 耗尽 B 细胞会损害脾 Tregs 的抗炎功能和心肌 Tregs 群体的平衡。此外，B 细胞可以将 CD4+CD25- T 细胞转化为 Foxp3+和 Foxp3-，这两种细胞均具有功能抑制性的 Treg 亚群。尽管 BKO 小鼠心肌炎症减少表明 B 细胞可能发挥促炎作用，但不能忽视 B 细胞的有益方面，即通过维持 Treg 数量来控制自身免疫。在 VMC 动物模型中观察到的结果突出了利妥昔单抗在非选择性耗尽 B 细胞的临床应用中的潜在危害。
