Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642.
Department of Environmental Medicine, University of Rochester, Rochester, NY 14642; and.
J Immunol. 2018 Dec 1;201(11):3343-3351. doi: 10.4049/jimmunol.1700503. Epub 2018 Oct 22.
Vaccination has been the most effective way to prevent or reduce infectious diseases; examples include the eradication of smallpox and attenuation of tetanus and measles. However, there is a large segment of the population that responds poorly to vaccines, in part because they are immunocompromised because of disease, age, or pharmacologic therapy and are unable to generate long-term protection. Specialized proresolving mediators are endogenously produced lipids that have potent proresolving and anti-inflammatory activities. Lipoxin B (LXB) is a member of the lipoxin family, with its proresolving effects shown in allergic airway inflammation. However, its effects on the adaptive immune system, especially on human B cells, are not known. In this study, we investigated the effects of LXB on human B cells using cells from healthy donors and donors vaccinated against influenza virus in vitro. LXB promoted IgG Ab production in memory B cells and also increased the number of IgG-secreting B cells. LXB enhanced expression of two key transcription factors involved in plasma cell differentiation, BLIMP1 and XBP1. Interestingly, LXB increased expression of cyclooxygenase-2 (COX2), an enzyme that is required for efficient B cell Ab production. The effects of LXB are at least partially COX2-dependent as COX2 inhibitors attenuated LXB-stimulated BLIMP1 and Xpb-1 expression as well as IgG production. Thus, our study reveals for the first time, to our knowledge, that LXB boosts memory B cell activation through COX2 and suggests that LXB can serve as a new vaccine adjuvant.
疫苗接种一直是预防或减少传染病最有效的方法；例如，天花已被根除，破伤风和麻疹的发病率也有所降低。然而，很大一部分人群对疫苗的反应不佳，部分原因是他们因疾病、年龄或药物治疗而免疫功能低下，无法产生长期保护。特殊的促解决介质是内源性产生的脂质，具有强大的促解决和抗炎活性。脂氧素 B（LXB）是脂氧素家族的一员，其在过敏性气道炎症中的促解决作用已得到证实。然而，它对适应性免疫系统的影响，特别是对人类 B 细胞的影响尚不清楚。在这项研究中，我们使用来自健康供体和接种流感病毒疫苗供体的细胞在体外研究了 LXB 对人类 B 细胞的影响。LXB 促进了记忆 B 细胞中 IgG Ab 的产生，也增加了 IgG 分泌 B 细胞的数量。LXB 增强了两个关键转录因子的表达，这两个转录因子参与浆细胞分化，分别是 BLIMP1 和 XBP1。有趣的是，LXB 增加了环氧化酶-2（COX2）的表达，COX2 是有效 B 细胞 Ab 产生所必需的酶。LXB 的作用至少部分依赖于 COX2，因为 COX2 抑制剂减弱了 LXB 刺激的 BLIMP1 和 Xpb-1 表达以及 IgG 的产生。因此，我们的研究首次揭示，据我们所知，LXB 通过 COX2 增强记忆 B 细胞的激活，并表明 LXB 可以作为一种新的疫苗佐剂。
