Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California, USA.
Department of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners, Irvine, California, USA.
J Virol. 2022 Mar 9;96(5):e0205721. doi: 10.1128/jvi.02057-21. Epub 2022 Jan 5.
Reactivation of herpes simplex virus 1 (HSV-1) from latently infected neurons of the trigeminal ganglia (TG) leads to blinding recurrent herpetic disease in symptomatic (SYMP) individuals. Although the role of T cells in herpes immunity seen in asymptomatic (ASYMP) individuals is heavily explored, the role of B cells is less investigated. In the present study, we evaluated whether B cells are associated with protective immunity against recurrent ocular herpes. The frequencies of circulating HSV-specific memory B cells and of memory follicular helper T cells (CD4 T cells), which help B cells produce antibodies, were compared between HSV-1-infected SYMP and ASYMP individuals. The levels of IgG/IgA and neutralizing antibodies were compared in SYMP and ASYMP individuals. We found that (i) the ASYMP individuals had increased frequencies of HSV-specific CD19CD27 memory B cells, and (ii) high frequencies of HSV-specific switched IgGCD19CD27 memory B cells detected in ASYMP individuals were directly proportional to high frequencies of CD45R0CXCR5CD4 memory T cells. However, no differences were detected in the level of HSV-specific IgG/IgA antibodies in SYMP and ASYMP individuals. Using the UV-B-induced HSV-1 reactivation mouse model, we found increased frequencies of HSV-specific antibody-secreting plasma HSV-1 gDCD138 B cells within the TG and circulation of ASYMP mice compared to those of SYMP mice. In contrast, no significant differences in the frequencies of B cells were found in the cornea, spleen, and bone-marrow. Our findings suggest that circulating antibody-producing HSV-specific memory B cells recruited locally to the TG may contribute to protection from symptomatic recurrent ocular herpes. Reactivation of herpes simplex virus 1 (HSV-1) from latently infected neurons of the trigeminal ganglia (TG) leads to blinding recurrent herpetic disease in symptomatic (SYMP) individuals. Although the role of T cells in herpes immunity against blinding recurrent herpetic disease is heavily explored, the role of B cells is less investigated. In the present study, we found that in both asymptomatic (ASYMP) individuals and ASYMP mice, there were increased frequencies of HSV-specific memory B cells that were directly proportional to high frequencies of memory T cells. Moreover, following UV-B-induced reactivation, we found increased frequencies of HSV-specific antibody-secreting plasma B cells within the TG and circulation of ASYMP mice compared to those of SYMP mice. Our findings suggest that circulating antibody-producing HSV-specific memory B cells recruited locally to the TG may contribute to protection from recurrent ocular herpes.
单纯疱疹病毒 1（HSV-1）从潜伏感染的三叉神经节（TG）神经元中重新激活，导致有症状（SYMP）个体出现致盲性复发性疱疹病。尽管 T 细胞在无症状（ASYMP）个体中对疱疹免疫的作用得到了广泛的研究，但 B 细胞的作用却研究较少。在本研究中，我们评估了 B 细胞是否与针对复发性眼部疱疹的保护性免疫有关。我们比较了 HSV-1 感染的 SYMP 和 ASYMP 个体之间循环中 HSV 特异性记忆 B 细胞和记忆滤泡辅助 T 细胞（CD4 T 细胞）的频率，这些细胞有助于 B 细胞产生抗体。我们发现：（i）ASYMP 个体中 HSV 特异性 CD19CD27 记忆 B 细胞的频率增加；（ii）在 ASYMP 个体中检测到的高频率 HSV 特异性转换 IgGCD19CD27 记忆 B 细胞与高频率 CD45R0CXCR5CD4 记忆 T 细胞直接相关。然而，在 SYMP 和 ASYMP 个体中，HSV 特异性 IgG/IgA 抗体的水平没有差异。使用 UV-B 诱导的 HSV-1 再激活小鼠模型，我们发现与 SYMP 小鼠相比，ASyMP 小鼠的 TG 和循环中 HSV 特异性抗体分泌的浆细胞 HSV-1 gDCD138 B 细胞的频率增加。相比之下，在角膜、脾脏和骨髓中，B 细胞的频率没有显著差异。我们的研究结果表明，循环中产生抗体的 HSV 特异性记忆 B 细胞可能有助于保护免受症状性复发性眼部疱疹。
