Prolactin alters the mechanisms of B cell tolerance induction.
Prolactin alters the mechanisms of B cell tolerance induction.
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DOI：
10.1002/art.24500
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发表时间：
2009-06
影响因子：
--
通讯作者：
Peeva, Elena
中科院分区：
文献类型：
--
作者：
Saha, Subhrajit;Gonzalez, Juana;Rosenfeld, Gabriel;Keiser, Harold;Peeva, Elena
自身免疫性疾病主要影响女性，这表明女性性激素可能在发病机制中发挥作用。我们以前已经表明，血清催乳素水平的持续轻度-中度升高会诱导BALB/c遗传背景小鼠的自我耐受性中断。在这项研究中，我们评估了高催乳素血症对B细胞耐受诱导机制的影响。本文研究了催乳素对雌性BalB/c小鼠脾B细胞亚群的影响。流式细胞术分析BCR介导的过渡期B细胞凋亡和增殖。通过基因芯片和实时荧光定量PCR检测凋亡基因的表达。通过流式细胞术和免疫组织化学评估κ/λ轻链共表达B细胞。通过BCR诱导的钙内流研究评价T3 B细胞的活化状态。BCR介导的T1 B细胞亚群凋亡，自身反应特异性阴性选择的主要检查点，在催乳素处理的小鼠中减少。微阵列研究表明，这一事件可能是由催乳素诱导的抗凋亡基因INF-γRII上调和促凋亡基因Trp 63下调介导的。催乳素处理还改变了受体编辑的量，如共表达κ/λ轻链的过渡性B细胞数量增加所示。此外，高催乳素血症通过增加T3 B细胞中BCR诱导的钙内流程度来改变B细胞无反应性的水平。持续升高的血清催乳素水平通过损害BCR介导的克隆缺失、解除受体编辑调节和降低无反应性B细胞活化阈值，从而促进自身反应性，干扰B细胞耐受诱导。
Autoimmune diseases predominantly affect women suggesting that female sex hormones may play a role in pathogenesis. We have previously shown that persistent mild-moderate elevations in serum prolactin levels induce a break in self-tolerance in mice with a BALB/c genetic background. In this study we evaluated the effects of hyperprolactinemia on mechanisms of B cell tolerance induction. Effects of prolactin on splenic B cell subsets were studied in female Balb/c mice. BCR-mediated apoptosis and proliferation of transitional B cells were analyzed by flow-cytometry. Expression of apoptotic genes was examined by microarrays and real-time PCR. Kappa/lambda light chain-coexpressing B cells were assessed by flowcytometry and immunohistochemistry. Activation status of T3 B cells was evaluated by BCR-induced calcium influx studies. BCR-mediated apoptosis of the T1 B cell subset, a major checkpoint for negative selection of autoreactive specificities, was decreased in prolactin-treated mice. Microarray studies indicated that this event may be mediated by the prolactin-induced upregulation of the anti-apoptotic gene INF-γRII and downregulation of the pro-apoptotic gene Trp63. Prolactin treatment also altered the amount of receptor editing as indicated by the increased number of transitional B cells co-expressing kappa/lambda light chains. Additionally, hyperprolactinemia modified the level of B cell anergy by increasing the degree of BCR-induced calcium influx in the T3 B cells. Persistently elevated serum prolactin levels interfere with B cell tolerance induction by impairing BCR-mediated clonal deletion, deregulating receptor editing, and decreasing the threshold for activation of anergic B cells, thereby promoting autoreactivity.
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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
DOI：
10.1073/pnas.040577497
发表时间：
2000-03-14
影响因子：
11.1
作者：
Bynoe, MS;Grimaldi, CM;Diamond, B
通讯作者：
Diamond, B
影响因子：
2.2
作者：
LYONS, AB;PARISH, CR
通讯作者：
PARISH, CR
影响因子：
9.2
作者：
EHLICH, A;MARTIN, V;RAJEWSKY, K
通讯作者：
RAJEWSKY, K
影响因子：
2.2
作者：
DESTGROTH, SF;SCHEIDEGGER, D
通讯作者：
SCHEIDEGGER, D