The Yaa Mutation Promoting Murine Lupus Causes Defective Development of Marginal Zone B Cells1
The Yaa Mutation Promoting Murine Lupus Causes Defective Development of Marginal Zone B Cells1
复制标题
促进小鼠狼疮的 Yaa 突变导致边缘区 B 细胞发育缺陷1
作者：
H. Amano;E. Amano;T. Moll;D. Marinkovic;N. Ibnou‐Zekri;E. Martínez;I. Semac;T. Wirth;L. Nitschke;S. Izui
BXSB雄性小鼠系统性红斑狼疮（SLE）的加速发展与一种尚未鉴定的突变基因Yaa（Y连锁自身免疫加速）的存在有关。鉴于边缘区（MZ）B细胞在小鼠SLE中可能的作用，我们探讨了Yaa突变的表达是否影响MZ和滤泡B细胞的分化，从而暗示疾病的加速。在这项研究中，我们表明，BXSB和C57 BL/6 Yaa小鼠，包括两个不同的亚系的BXSB Yaa男性是保护SLE，显示受损的发展MZ B细胞在生命早期。对骨髓嵌合体的研究表明，MZ B细胞的丢失是由于表达Yaa突变的B细胞的内在缺陷所致。在患病的BXSB Yaa雄性中缺乏MZ B细胞的选择性扩增，强烈反对MZ B细胞在SLE的BXSB模型中产生致病性自身抗体中的主要作用。此外，与CD 22缺陷或表达IgM抗三硝基苯基/DNA转基因的小鼠的比较分析表明，Yaa B细胞的高反应性表型，如通过显著增加的自发IgM分泌所判断的，可能有助于向滤泡B细胞成熟的增强和MZ B细胞生成的阻断。
The accelerated development of systemic lupus erythematosus (SLE) in BXSB male mice is associated with the presence of an as yet unidentified mutant gene, Yaa (Y-linked autoimmune acceleration). In view of a possible role of marginal zone (MZ) B cells in murine SLE, we have explored whether the expression of the Yaa mutation affects the differentiation of MZ and follicular B cells, thereby implicating the acceleration of the disease. In this study, we show that both BXSB and C57BL/6 Yaa mice, including two different substrains of BXSB Yaa males that are protected from SLE, displayed an impaired development of MZ B cells early in life. Studies in bone marrow chimeras revealed that the loss of MZ B cells resulted from a defect intrinsic to B cells expressing the Yaa mutation. The lack of selective expansion of MZ B cells in diseased BXSB Yaa males strongly argues against a major role of MZ B cells in the generation of pathogenic autoantibodies in the BXSB model of SLE. Furthermore, a comparative analysis with mice deficient in CD22 or expressing an IgM anti-trinitrophenyl/DNA transgene suggests that the hyperreactive phenotype of Yaa B cells, as judged by a markedly increased spontaneous IgM secretion, is likely to contribute to the enhanced maturation toward follicular B cells and the block in the MZ B cell generation.
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影响因子：
4.4
作者：
A. Oliver;F. Martin;J. Kearney
通讯作者：
A. Oliver;F. Martin;J. Kearney
影响因子：
32.4
作者：
Cariappa, A;Tang, M;Pillai, S
通讯作者：
Pillai, S
影响因子：
4.4
作者：
Masahiko Amano;Nicole Baumgarth;M. Dick;L. Brossay;Mitchell Kronenberg;Leonard A. Herzenberg;S. Strober
通讯作者：
Masahiko Amano;Nicole Baumgarth;M. Dick;L. Brossay;Mitchell Kronenberg;Leonard A. Herzenberg;S. Strober
影响因子：
32.4
作者：
Martin, F;Kearney, JF
通讯作者：
Kearney, JF
影响因子：
4.4
作者：
Chen, XJ;Martin, F;Kearney, JF
通讯作者：
Kearney, JF