Lang Gillian A, Amadou Amani Souwelimatou, Quinn James L, Axtell Robert C, Lang Mark L
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104; and.
Oklahoma Medical Research Foundation, Oklahoma City, OK 73104.
Immunohorizons. 2019 Mar;3(3):88-93. doi: 10.4049/immunohorizons.1800081.
The CD1d-binding glycolipid α-galactosylceramide (α-GC) is a potent adjuvant that activates NKT cells and in turn enhances T-dependent humoral immunity. Very little is known about how NKT cells and the NKT follicular helper (NKTfh) subset influence the immune response to T-independent polysaccharides. In this study, we used a Cre-Lox approach to generate mice devoid of the master transcription factor in CD4 lineage cells and thus devoid of NKTfh cells but not total NKT cells. It was observed that α-GC-driven IgG1 class switch against a polysaccharide Ag was dependent on the NKTfh subset. However, α-GC was unable to stimulate a polysaccharide-specific Ab recall response. It was observed that NKT-derived IL-21 was able to exert limited influence on the IgG1 response and was therefore likely to work in concert with other factors. This work shows that α-GC-driven NKTfh cells can direct polysaccharide-specific B cell responses by promoting IgG1 class switch but do not provide signals needed for generation of polysaccharide-specific B cell memory.
与CD1d结合的糖脂α-半乳糖神经酰胺（α-GC）是一种有效的佐剂，可激活自然杀伤T细胞（NKT细胞），进而增强T细胞依赖性体液免疫。关于NKT细胞和NKT滤泡辅助细胞（NKTfh）亚群如何影响对T细胞非依赖性多糖的免疫反应，目前所知甚少。在本研究中，我们采用Cre-Lox方法培育出在CD4谱系细胞中缺乏主转录因子，因而缺乏NKTfh细胞但不缺乏总NKT细胞的小鼠。我们观察到，α-GC驱动的针对多糖抗原的IgG1类别转换依赖于NKTfh亚群。然而，α-GC无法刺激多糖特异性抗体的回忆反应。我们观察到，NKT细胞衍生的白细胞介素-21（IL-21）对IgG1反应的影响有限，因此可能与其他因素协同发挥作用。这项研究表明，α-GC驱动的NKTfh细胞可通过促进IgG1类别转换来指导多糖特异性B细胞反应，但无法提供产生多糖特异性B细胞记忆所需的信号。
