Salmonella SiiE prevents an efficient humoral immune memory by interfering with IgG+ plasma cell persistence in the bone marrow
Salmonella SiiE prevents an efficient humoral immune memory by interfering with IgG+ plasma cell persistence in the bone marrow
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DOI：
10.1073/pnas.1818242116
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发表时间：
2019-04-09
影响因子：
11.1
通讯作者：
Tokoyoda, Koji
中科院分区：
文献类型：
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作者：
Maenne, Christian;Takaya, Akiko;Tokoyoda, Koji
血清免疫球蛋白主要由骨髓中分泌免疫球蛋白的浆细胞产生，保护我们的身体免受各种病原体的侵袭。我们在这里表明，沙门氏菌的SIIE蛋白既是必需的，也是足够的，通过选择性地减少骨髓中分泌免疫球蛋白的浆细胞的数量，防止对病原体的有效体液免疫记忆。减毒的SiiE缺陷沙门氏菌能诱导高滴度和持久的沙门氏菌特异性和保护性的免疫球蛋白，是一种有效的沙门氏菌疫苗。一种与层粘连蛋白β1同源的SiIE衍生多肽足以去除骨髓中分泌免疫球蛋白G的浆细胞，确定层粘连蛋白β1是骨髓中分泌免疫球蛋白的浆细胞的一个组成部分，而且，它是选择性去除自身免疫性疾病和多发性骨髓瘤中分泌免疫球蛋白的浆细胞的唯一治疗选择。
Serum IgG, which is mainly generated from IgG-secreting plasma cells in the bone marrow (BM), protects our body against various pathogens. We show here that the protein SiiE of Salmonella is both required and sufficient to prevent an efficient humoral immune memory against the pathogen by selectively reducing the number of IgG-secreting plasma cells in the BM. Attenuated SiiE-deficient Salmonella induces high and lasting titers of specific and protective Salmonella-specific IgG and qualifies as an efficient vaccine against Salmonella. A SiiE-derived peptide with homology to laminin beta 1 is sufficient to ablate IgG-secreting plasma cells from the BM, identifying laminin beta 1 as a component of niches for IgG-secreting plasma cells in the BM, and furthermore, qualifies it as a unique therapeutic option to selectively ablate IgG-secreting plasma cells in autoimmune diseases and multiple myeloma.