Optimal germinal center B cell activation and T-dependent antibody responses require expression of the mouse complement receptor Cr1.
Optimal germinal center B cell activation and T-dependent antibody responses require expression of the mouse complement receptor Cr1.
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DOI：
10.4049/jimmunol.1203176
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发表时间：
2013-07-01
期刊：
影响因子：
--
通讯作者：
Weis JH
中科院分区：
文献类型：
--
作者：
Donius LR;Handy JM;Weis JJ;Weis JH
滤泡树突状细胞和补体受体1和2对体液免疫的产生起重要作用。研究表明，B细胞和FDC上CR1/2的表达为B细胞的激活提供了二次信号，促进了抗原在免疫滤泡中的运输，并增强了FDC对免疫复合体的保留。我们在这里表明，小鼠B细胞主要表达Cr2基因的Cr2产物，而FDC几乎只表达Cr2基因产生的CR1亚型。为了确定CR1的特定作用，我们创造了一种动物，它保持正常细胞限制的CR2表达，但不表达CR1。CR1缺陷(Cr1KO)小鼠发育出正常的B1和B2未成熟和成熟的B细胞亚群，并具有正常水平的幼稚血清抗体，但天然抗体水平发生变化。对Cr1KO动物的免疫表现出对T依赖的但不是T非依赖的抗原的抗体反应不足。免疫的Cr1KO动物的生发中心缺乏激活的B细胞，这与缺乏CR1和Cr2或C3的动物相似。最后，缺乏CR1的动物对肺炎链球菌感染的反应与WT动物相似，肺炎链球菌是一种缺乏C3或同时缺乏CR1和Cr2的动物对肺炎链球菌特别敏感的病原体。总之，这些数据表明，主要由FDC产生的CR1在生发中心适当激活的B细胞的产生和成熟抗体反应的产生中起关键作用。
Follicular dendritic cells and complement receptors 1 and 2 are important for the generation of humoral immunity. Cr1/2 expression on B cells and FDC has been shown to provide a secondary signal for B cell activation, to facilitate transport of antigen in immune follicles, and to enhance retention of immune complexes by FDC. We show here that murine B cells predominantly express the Cr2 product from the Cr2 gene while FDC nearly exclusively express the Cr1 isoform generated from the Cr2 gene. To define the specific role of Cr1, we have created an animal that maintains normal cell restricted expression of Cr2 but does not express Cr1. Cr1 deficient (Cr1KO) mice develop normal B1 and B2 immature and mature B cell subsets, and have normal levels of naïve serum antibodies but altered levels of natural antibodies. Immunization of the Cr1KO animal demonstrates deficient antibody responses to T-dependent but not T-independent antigens. Germinal centers from the immunized Cr1KO animal possess a deficiency in activated B cells, similar to that seen for the animal lacking both Cr1 and Cr2, or C3. Finally, animals lacking only Cr1 respond similar to the WT animal to infections with Streptococcus pneumoniae, a pathogen that animals lacking C3 or both Cr1 and Cr2 are particularly sensitive to. These data, in total, suggest that the production of Cr1 primarily by FDC is critical in the generation of appropriately activated B cells of the germinal center and the generation of mature antibody responses.
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影响因子：
15.3
作者：
Pepys, M B
通讯作者：
Pepys, M B
DOI：
10.4049/jimmunol.181.5.2953
发表时间：
2008-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jacobson AC;Weis JH
通讯作者：
Weis JH
影响因子：
4.4
作者：
Hasegawa, M;Fujimoto, M;Tedder, TF
通讯作者：
Tedder, TF
影响因子：
32.4
作者：
Haas, KM;Hasegawa, M;Tedder, TF
通讯作者：
Tedder, TF
影响因子：
5.3
作者：
Naito, Yuko;Takematsu, Hiromu;Kozutsumi, Yasunori
通讯作者：
Kozutsumi, Yasunori