Birrell Louise, Kulik Liudmila, Morgan B Paul, Holers V Michael, Marchbank Kevin J
Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, UK.
J Immunol. 2005 Jun 1;174(11):6974-82. doi: 10.4049/jimmunol.174.11.6974.
Complement receptor type 2 (CR2/CD21), in association with CD19, plays an important role in enhancing mature B cell responses to opsonized Ags. We have shown that mice expressing a human CR2/CD21 (hCR2/CD21) transgene during the CD43(+)/CD25(-) late pro-B cell stage of B cell development demonstrate marked changes in subsequent B cell ontogeny. In the present study, we show that the humoral immune response to the T cell-dependent Ag, sheep RBC, is muted severely in a manner inversely proportional to B cell expression level of hCR2. Individual Ag-specific IgG isotypes vary in the degree to which they are affected but all are reduced while IgM titers are normal. A substantial reduction in germinal centers, both in size and frequency, in the spleens of immunized hCR2 transgenic mice demonstrates a failure to maintain germinal center reaction. However, both IgM expression levels and LPS-proliferative responses appear fully intact in B cells from hCR2-positive mice, suggesting that this alteration in B cell phenotype is different qualitatively from that of specific Ag-defined anergy models. These data suggest that the unresponsiveness to T-dependent Ags displayed by hCR2-positive B cells is linked to an increase in the level of stimulus required to propel the B cell into a fully activated state and thus a normal humoral immune response to Ags. We conclude that this phenotype and these mice may offer an additional means to dissect mechanisms underlying B cell tolerance and Ag responsiveness both in bone marrow and periphery.
补体受体2型（CR2/CD21）与CD19协同作用，在增强成熟B细胞对调理素化抗原的反应中发挥重要作用。我们已经表明，在B细胞发育的CD43(+)/CD25(-)晚期前B细胞阶段表达人CR2/CD21（hCR2/CD21）转基因的小鼠，在随后的B细胞个体发育中表现出明显变化。在本研究中，我们发现，对T细胞依赖性抗原绵羊红细胞的体液免疫反应严重减弱，其减弱程度与hCR2在B细胞中的表达水平成反比。各个抗原特异性IgG同种型受影响的程度不同，但所有同种型均减少，而IgM滴度正常。免疫的hCR2转基因小鼠脾脏中生发中心的大小和频率均大幅降低，表明无法维持生发中心反应。然而，hCR2阳性小鼠的B细胞中IgM表达水平和LPS增殖反应似乎完全正常，这表明B细胞表型的这种改变在性质上不同于特定抗原定义的无反应性模型。这些数据表明，hCR2阳性B细胞对T依赖性抗原的无反应性与推动B细胞进入完全激活状态所需的刺激水平增加有关，从而与对抗原的正常体液免疫反应有关。我们得出结论，这种表型和这些小鼠可能为剖析骨髓和外周中B细胞耐受性和抗原反应性的潜在机制提供额外手段。
