Developmental acquisition of the Lyn-CD22-SHP-1 inhibitory pathway promotes B cell tolerance.
Developmental acquisition of the Lyn-CD22-SHP-1 inhibitory pathway promotes B cell tolerance.
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DOI：
10.4049/jimmunol.0803941
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发表时间：
2009-05-01
期刊：
影响因子：
--
通讯作者：
DeFranco AL
中科院分区：
文献类型：
--
作者：
Gross AJ;Lyandres JR;Panigrahi AK;Prak ET;DeFranco AL
为了更好地了解 Lyn 缺陷小鼠的自身免疫是否源于中枢或外周 B 细胞耐受性受损，我们检查了野生型和 Lyn 缺陷 B 细胞在不同发育阶段的 BCR 信号传导特性。就 BCR 诱导的钙升高和 Erk MAP 激酶激活而言，野生型成熟滤泡 B 细胞对 BCR 刺激的敏感性低于未成熟 T1 B 细胞。在缺乏 Lyn 的情况下，成熟 B 细胞信号传导大大增强，而未成熟 B 细胞信号传导受到的影响最小。相应地，Lyn 缺陷大大增强了成熟 B 细胞对 BCR 激活的敏感性，但对未成熟阶段耐受诱导相关事件的影响最小。 CD22 缺陷对 BCR 信号传导的影响在不同成熟阶段的 B 细胞中非常相似。这些结果表明，随着 B 细胞成熟，Lyn-CD22-SHP-1 抑制途径在很大程度上开始发挥作用，并设定了一个激活阈值，这对于维持 B 细胞区室的耐受性至关重要。
To better understand whether autoimmunity in Lyn-deficient mice arises from compromised central or peripheral B cell tolerance, we examined BCR signaling properties of wild type and Lyn-deficient B cells at different stages of development. Wild-type mature follicular B cells were less sensitive to BCR stimulation than were immature T1 B cells with regard to BCR-induced calcium elevation and Erk MAP kinase activation. In the absence of Lyn, mature B cell signaling was greatly enhanced, whereas immature B cell signaling was minimally affected. Correspondingly, Lyn-deficiency substantially enhanced the sensitivity of mature B cells to activation via the BCR, but minimally affected events associated with tolerance induction at the immature stage. The effects of CD22-deficiency on BCR signaling were very similar in B cells at different stages of maturation. These results indicate that the Lyn–CD22–SHP-1 inhibitory pathway largely becomes operational as B cell mature and sets a threshold for activation that appears to be critical for the maintenance of tolerance in the B cell compartment.
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脾脏中的B细胞发育发生在离散的步骤中，并取决于B细胞受体衍生的信号的质量。
影响因子：
15.3
作者：
Loder, F;Mutschler, B;Ray, R J;Paige, C J;Sideras, P;Torres, R;Lamers, M C;Carsetti, R
通讯作者：
Carsetti, R
影响因子：
4.4
作者：
Erickson, LD;Tygrett, LT;Waldschmidt, TJ
通讯作者：
Waldschmidt, TJ
影响因子：
20.3
作者：
Lindsley, Robert Coleman;Thomas, Matthew;Allman, David
通讯作者：
Allman, David
影响因子：
32.4
作者：
Cornall, RJ;Cyster, JG;Goodnow, CC
通讯作者：
Goodnow, CC
影响因子：
15.3
作者：
O'Keefe, T L;Williams, G T;Batista, F D;Neuberger, M S
通讯作者：
Neuberger, M S