Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, NO-0372 Oslo, Norway.
Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, NO-0372 Oslo, Norway; Proteomics Core Facility, Oslo University Hospital-Rikshospitalet, NO-0372 Oslo, Norway.
Cell Rep. 2017 Sep 5;20(10):2357-2367. doi: 10.1016/j.celrep.2017.08.036.
Mucosal antigens induce generation of lamina propria plasma cells (PCs) that secrete dimeric immunoglobulin A (IgA) destined for transport across the epithelium. In addition, blood contains monomeric IgA. To study the relationship between mucosal and systemic antibody responses, we took advantage of celiac disease patient samples for isolation of gut PCs as well as serum IgA and IgG reactive with a gluten-derived peptide or the autoantigen transglutaminase 2. Proteomic analysis of serum IgA revealed antigen-specific V-gene preferences, which matched those found in gut PCs. Further, gut PC CDR-H3 sequences were abundant in serum IgA but also detectable in serum IgG. Our data indicate that the same B cell clones that give rise to gut PCs also contribute to the serum antibody pool. However, serum IgA antibodies had a molecular composition distinct from that of IgA antibodies secreted in the gut, suggesting that individual B cell clones give rise to different PC populations.
黏膜抗原诱导固有层浆细胞（PCs）产生，这些细胞分泌二聚体免疫球蛋白 A（IgA），用于穿过上皮细胞运输。此外，血液中还含有单体 IgA。为了研究黏膜和系统性抗体反应之间的关系，我们利用乳糜泻患者的样本分离肠道 PCs，以及与谷蛋白衍生肽或自身抗原转谷氨酰胺酶 2 反应的血清 IgA 和 IgG。血清 IgA 的蛋白质组学分析显示了抗原特异性 V 基因偏好，与肠道 PCs 中发现的偏好相匹配。此外，肠道 PC 的 CDR-H3 序列在血清 IgA 中丰富，在血清 IgG 中也可检测到。我们的数据表明，产生肠道 PCs 的相同 B 细胞克隆也有助于血清抗体库。然而，血清 IgA 抗体的分子组成与肠道中分泌的 IgA 抗体不同，这表明单个 B 细胞克隆产生不同的 PC 群体。
