Department of Microbial Pathogens and Immunity, Rush University Medical Centergrid.240684.c, Chicago, Illinois, USA.
J Virol. 2022 Apr 13;96(7):e0023522. doi: 10.1128/jvi.00235-22. Epub 2022 Mar 21.
Here, we report the appearance of natural killer B (NKB) cells within the colon during simian immunodeficiency virus (SIV) infection of susceptible monkeys. Using RNA sequencing (RNAseq) and flow cytometry, we show that NKB cells are unique cells with features and functions of both NK and B cells. NKB cells express receptors and ligands found on B cells that are important for (i) antigen presentation; (ii) activities associated with class switching, affinity maturation, and B-cell memory formation in secondary lymphoid follicles; and (iii) antigen recognition. The predominant immunoglobulins (Igs) expressed on NKB cells are IgA, although NKB cells can express surface IgM and IgG. There is dominant lambda expression over the kappa light chain characteristic of mucosal B cells. In addition to B-cell aspects, NKB cells express NK cell activation receptors and Fas ligand. We show in this study that NKB cells express perforin and granzymes and lyse cells in a lytic assay. In addition to NK cell cytolytic function, NKB cells also produce the inflammatory cytokines interferon gamma, tumor necrosis factor alpha, and interleukin-18 (IL-18). Finally, we noted the increased capacity of NKB cells to proliferate compared to NK cells and CD8 T cells from the SIV-infected colon. The increased proliferation and inflammatory cytokine production may be related to the relatively high expression levels of IL-15 receptor beta, IL-7 receptor, IL-18 receptor, and 41BB relative to the same receptors on CD8 and NK cells. The properties of NKB cells may point to their role in the enhanced inflammation observed in the SIV-infected gut. There is low-level but significant mucosal inflammation in the gastrointestinal tract secondary to human immunodeficiency virus (HIV) infection that has long-term consequences for the infected host. This inflammation most likely originates from the immune response that appears as a consequence of HIV. Here, we show in an animal model of HIV that the chronically SIV-infected gut contains cytotoxic natural killer B cells that produce inflammatory cytokines and proliferate during infection.
在这里，我们报告了在易感猴子感染猴免疫缺陷病毒（SIV）期间，自然杀伤 B（NKB）细胞出现在结肠中。使用 RNA 测序（RNAseq）和流式细胞术，我们表明 NKB 细胞是具有 NK 和 B 细胞特征和功能的独特细胞。NKB 细胞表达 B 细胞上的受体和配体，这些受体和配体对于（i）抗原呈递；（ii）与次级淋巴滤泡中的类别转换、亲和力成熟和 B 细胞记忆形成相关的活动；和（iii）抗原识别很重要。NKB 细胞上表达的主要免疫球蛋白（Igs）是 IgA，尽管 NKB 细胞也可以表达表面 IgM 和 IgG。存在主导的免疫球蛋白轻链 λ表达，而不是粘膜 B 细胞的 κ 轻链特征。除了 B 细胞方面，NKB 细胞还表达 NK 细胞激活受体和 Fas 配体。在本研究中，我们表明 NKB 细胞表达穿孔素和颗粒酶，并在裂解测定中裂解细胞。除了 NK 细胞细胞溶解功能外，NKB 细胞还产生炎症细胞因子干扰素 γ、肿瘤坏死因子 α 和白细胞介素-18（IL-18）。最后，我们注意到与 SIV 感染结肠中的 NK 细胞和 CD8 T 细胞相比，NKB 细胞的增殖能力增加。与 CD8 和 NK 细胞上相同受体相比，NKB 细胞中 IL-15 受体 β、IL-7 受体、IL-18 受体和 41BB 的相对高表达水平可能与增加的增殖和炎症细胞因子产生有关。NKB 细胞的特性可能表明它们在 SIV 感染肠道中观察到的增强炎症中发挥作用。继发于人类免疫缺陷病毒（HIV）感染的胃肠道存在低水平但显著的粘膜炎症，对受感染宿主有长期影响。这种炎症很可能源自作为 HIV 后果出现的免疫反应。在这里，我们在 HIV 动物模型中表明，慢性 SIV 感染的肠道含有细胞毒性自然杀伤 B 细胞，这些细胞在感染期间产生炎症细胞因子并增殖。
