Analysis of marginal zone B cell development in the mouse with limited B cell diversity: Role of the antigen receptor signals in the recruitment of B cells to the marginal zone
Analysis of marginal zone B cell development in the mouse with limited B cell diversity: Role of the antigen receptor signals in the recruitment of B cells to the marginal zone
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DOI：
10.4049/jimmunol.174.3.1438
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发表时间：
2005-02-01
影响因子：
4.4
通讯作者：
Ohmori, H
中科院分区：
文献类型：
--
作者：
Kanayama, N;Cascalho, M;Ohmori, H
准单克隆（QM）小鼠提供了一种可理解的模型，用于分析B细胞选择，即两种主要的4-羟基-3-硝基苯乙酰特异性B细胞群体之间的竞争，其BCR由敲入V（H）17.2.25（VHT）编码的H链和p53 da 1或p53 da 2 L链组成。在这项研究中，我们显示QM系统是有用的，以检查如何BCR信号引导一个子集的B细胞的边缘区（MZ）。与对照C57 BL/6小鼠相比，QM小鼠具有类似于2.7倍的增加的表现出MZ B细胞表型的B细胞数量和更大的MZ面积。有趣的是，在MZ-（VHT/Bunda 1：VHT/Bunda 2约为3：7）和过渡型2-B细胞亚群中，VHT/Bunda 2 B细胞显著优于VHT/Bunda 1 B细胞，而这两个群体在未成熟、过渡型1和成熟对应物中相当。因此，在MZ B细胞中有偏向地使用pcda 2可能是外围选择的结果。MZ B细胞区室的扩大和VHT/（lambda）2 B细胞的优先募集通过加倍VHT基因而进一步增强，但受到布鲁顿酪氨酸激酶功能障碍的抑制，这表明BCR信号在该选择中的积极作用。比较VHT/IgG 1和VHT/IgG 2 IgM mAb的Ag特异性，发现VHT/IgG 2 BCR具有多反应性，包括与ssDNA的反应性。综上所述，表明BCR的多反应性（包括自身反应性）在驱动B细胞分化为MZ表型中至关重要。
The quasimonoclonal (QM) mouse provides an intelligible model to analyze the B cell selection as the competition between two major 4-hydroxy-3-nitrophenylacetyl-specific B cell populations whose BCR are comprised of the knockin V(H)17.2.25 (VHT)encoded H chain and the lambda1 or lambda2 L chain. In this study, we show the QM system is useful to examine how BCR signals guide a subset of B cells to the marginal zone (MZ). Compared with the control C57BL/6 mice, the QM mice had similar to2.7-fold increased number of B cells exhibiting the MZ B cell phenotype and a larger MZ area in the spleen. Interestingly, VHT/lambda2 B cells significantly predominated over VHT/lambda1 B cells in MZ-(VHT/lambda1:VHT/lambda2 approximate to 3:7) and transitional 2-B cell subsets, while these two populations were comparable in immature, transitional 1, and mature counterparts. Thus, the biased use of lambda2 in the MZ B cells may be the result of selection in the periphery. The enlargement of MZ B cell compartment and the preferred recruitment of the VHT/(lambda)2 B cells were further augmented by doubling the VHT gene, but dampened by the dysfunction of Bruton's tyrosine kinase, suggesting a positive role of BCR signaling in this selection. Comparison of Ag specificity between VHT/lambda1 and VHT/lambda2 IgM mAbs revealed a polyreactive nature of the VHT/lambda2 BCR, including the reactivity with ssDNA. Taken together, it is suggested that polyreactivity (including self-reactivity) of BCR is crucial in driving B cells to differentiate into the MZ phenotype.