CD83 Modulates B Cell Activation and Germinal Center Responses
CD83 Modulates B Cell Activation and Germinal Center Responses
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DOI：
10.4049/jimmunol.1502163
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发表时间：
2016-05-01
影响因子：
4.4
通讯作者：
Nitschke, Lars
中科院分区：
文献类型：
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作者：
Krzyzak, Lena;Seitz, Christine;Nitschke, Lars
CD83是树突状细胞的成熟标志物。在B细胞谱系中，CD 83在生发中心（GC）反应期间尤其在活化的B细胞和亮区B细胞上表达。CD83在GC反应中的功能尚不清楚。CD 83（-/-）小鼠具有CD 4（+）T细胞的强烈减少，这使得难以分析GC应答期间CD 83对B细胞的功能作用。因此，在本研究中，我们产生了B细胞特异性CD 83条件性敲除（CD 83 B-cKO）模型。CD83 B-cKO B细胞在不同刺激后显示出MHC II类和CD86表达的缺陷性上调以及受损的增殖。用各种Ag免疫后GC应答的分析揭示了暗区和亮区B细胞数量的特征性转变，其中在CD 83 B-cKO小鼠的暗区中B细胞增加。这种效应并不伴随IgG免疫应答水平的改变或亲和力成熟的主要差异。然而，在CD83 B-cKO小鼠中观察到增强的IgE应答。此外，我们观察到在混合骨髓嵌合体中，CD 83-cKO B细胞在GC应答中具有强烈的竞争劣势。此外，用伯氏疏螺旋体感染小鼠揭示了CD83 B-cKO小鼠的细菌清除缺陷，向Th2应答转变，这由IgE滴度的强烈增加指示。总之，我们的结果表明，CD83是重要的B细胞活化和调节GC组成和IgE抗体反应在体内。
CD83 is a maturation marker for dendritic cells. In the B cell lineage, CD83 is expressed especially on activated B cells and on light zone B cells during the germinal center (GC) reaction. The function of CD83 during GC responses is unclear. CD83(-/-) mice have a strong reduction of CD4(+) T cells, which makes it difficult to analyze a functional role of CD83 on B cells during GC responses. Therefore, in the present study we generated a B cell-specific CD83 conditional knockout (CD83 B-cKO) model. CD83 B-cKO B cells show defective upregulation of MHC class II and CD86 expression and impaired proliferation after different stimuli. Analyses of GC responses after immunization with various Ags revealed a characteristic shift in dark zone and light zone B cell numbers, with an increase of B cells in the dark zone of CD83 B-cKO mice. This effect was not accompanied by alterations in the level of IgG immune responses or by major differences in affinity maturation. However, an enhanced IgE response was observed in CD83 B-cKO mice. Additionally, we observed a strong competitive disadvantage of CD83-cKO B cells in GC responses in mixed bone marrow chimeras. Furthermore, infection of mice with Borrelia burgdorferi revealed a defect in bacterial clearance of CD83 B-cKO mice with a shift toward a Th2 response, indicated by a strong increase in IgE titers. Taken together, our results show that CD83 is important for B cell activation and modulates GC composition and IgE Ab responses in vivo.