Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway.
KG Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, Norway.
United European Gastroenterol J. 2019 Dec;7(10):1399-1407. doi: 10.1177/2050640619862461. Epub 2019 Jul 3.
Plasma cells (PCs) are terminally differentiated B-lymphocytes producing antibodies. In coeliac disease (CeD) there is increased density of PCs in the small-intestinal lesion. Many of these PCs produce disease-specific autoantibodies targeting transglutaminase 2 (TG2).
The plasmacytosis of CeD motivated us to study the transcriptional programme of PCs from coeliac gut lesions.
RNA-seq was performed on the PCs of CeD patients and disease controls, being specific or non-specific for TG2.
Being antibody-producing cells, 67% of the PCs' transcript was aligned to immunoglobulin genes. Strikingly, genes encoding ligands and receptors of chemokines and cytokines were abundant. Higher transcript levels of genes associated with cell activation and immune responses were observed in PCs of CeD patients compared to controls. TG2-specific compared to non-TG2 specific PCs expressed increased levels of CXCR3, CXCL10 and interleukin-15; factors that have been implicated in the pathogenesis of CeD yet with production attributed to other cells than PCs. The presence of transcripts of HLA class II and T-cell co-stimulatory molecules suggests that PCs may serve as antigen-presenting cells for CD4 + helper T cells.
Our findings shed new light on the biology of intestinal PCs, implicating functions that go beyond the production of immunoglobulins.
浆细胞（PCs）是终末分化的 B 淋巴细胞，能够产生抗体。在乳糜泻（CeD）中，小肠病变中 PC 的密度增加。这些 PC 中的许多产生针对转谷氨酰胺酶 2（TG2）的疾病特异性自身抗体。
CeD 中的浆细胞增多促使我们研究来自乳糜泻肠道病变的 PC 的转录程序。
对 CeD 患者和疾病对照者的 PCs 进行 RNA-seq 分析，这些 PC 针对 TG2 具有特异性或非特异性。
作为产生抗体的细胞，67%的 PC 转录物与免疫球蛋白基因对齐。引人注目的是，编码趋化因子和细胞因子配体和受体的基因丰富。与对照组相比，CeD 患者的 PC 中与细胞激活和免疫反应相关的基因转录水平更高。与非 TG2 特异性 PC 相比，TG2 特异性 PC 表达了更高水平的 CXCR3、CXCL10 和白细胞介素 15；这些因子已被牵连到 CeD 的发病机制中，但被认为是除 PC 以外的其他细胞产生的。HLA Ⅱ类和 T 细胞共刺激分子的转录本的存在表明 PC 可能作为 CD4+辅助 T 细胞的抗原呈递细胞。
我们的发现为肠道 PCs 的生物学提供了新的见解，暗示了超出产生免疫球蛋白的功能。
