Mouse complement receptors type 1 (CR1;CD35) and type 2 (CR2;CD21): expression on normal B cell subpopulations and decreased levels during the development of autoimmunity in MRL/lpr mice.
Mouse complement receptors type 1 (CR1;CD35) and type 2 (CR2;CD21): expression on normal B cell subpopulations and decreased levels during the development of autoimmunity in MRL/lpr mice.
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DOI：
10.4049/jimmunol.159.3.1557
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发表时间：
1997-08
影响因子：
4.4
通讯作者：
K. Takahashi;Yuko Kozono;Thomas J. Waldschmidt;D. Berthiaume;R. Quigg;A. Baron;V. Holers
中科院分区：
文献类型：
--
作者：
K. Takahashi;Yuko Kozono;Thomas J. Waldschmidt;D. Berthiaume;R. Quigg;A. Baron;V. Holers
人补体受体1型（hCR 1; CD 35）和2型（hCR 2; CD 21）在分化和活化期间的特定阶段在B淋巴细胞上表达。这些受体在对T依赖性抗原的免疫应答中起关键作用，除了生发中心的形成。系统性红斑狼疮（SLE）患者B淋巴细胞hCR 2和hCR 1的表达均降低。我们研究了小鼠CR2和CR 1在BALB/c小鼠正常B淋巴细胞群上的表达。我们的研究结果表明，这些受体在正常状态下的表达密切平行的hCR 2。在骨髓发育过程中，首先在低B220/高IgM细胞上检测到表达，表明补体受体在中枢耐受机制完成后出现。在脾微环境中，在边缘区B淋巴细胞上发现最高水平的受体表达。除伊加+派伊尔集合淋巴结B细胞外，还在腹膜B1 a和B1 B细胞上发现小鼠CR 2和CR 1。在Th 2条件下脾B细胞的活化导致受体表达的显著降低。为了确定受体表达的模式是否也与人类疾病中发现的模式相似，我们研究了SLE的MRL lpr/lpr（MRL/lpr）模型。有趣的是，我们发现补体受体表达的早期降低是进行性的，并且在肾炎的主要临床表现之前首先可检测到。我们推测，补体受体表达的早期减少，如MRL/lpr小鼠表现出的在小鼠和人类SLE的发病机制中起着重要作用。
Human complement receptors type 1 (hCR1;CD35) and type 2 (hCR2;CD21) are expressed on B lymphocytes at specific stages during differentiation and activation. These receptors play critical roles in the immune response to T-dependent Ags in addition to germinal center formation. Expression of both hCR2 and hCR1 is decreased on B lymphocytes of patients with systemic lupus erythematosus (SLE). We have studied the expression of mouse CR2 and CR1 on normal populations of mouse B lymphocytes in BALB/c mice. Our results demonstrate that expression of these receptors in the normal state closely parallels that of hCR2. During bone marrow development, expression is first detected on low B220/high IgM cells, demonstrating that complement receptors appear after central tolerance mechanisms are completed. In the splenic microenvironment the highest levels of receptor expression are found on marginal zone B lymphocytes. Mouse CR2 and CR1 are also found on peritoneal B1a and B1b cells in addition to IgA+ Peyer's patch B cells. Activation of splenic B cells under Th2 conditions results in a marked decrease in receptor expression. To determine whether the patterns of receptor expression also parallel those found in human disease, we studied the MRL lpr/lpr (MRL/lpr) model of SLE. Interestingly, we found an early decrease in complement receptor expression that is progressive and first detectable before major clinical manifestations of nephritis. We hypothesize that the early decrease in complement receptor expression such as that demonstrated by MRL/lpr mice plays an important role in the pathogenesis of murine and perhaps human SLE.