Differential Activation of Anti-Erythrocyte and Anti-DNA Autoreactive B Lymphocytes by the Yaa Mutation1
Differential Activation of Anti-Erythrocyte and Anti-DNA Autoreactive B Lymphocytes by the Yaa Mutation1
复制标题
Yaa 突变对抗红细胞和抗 DNA 自身反应 B 淋巴细胞的差异激活1
作者：
T. Moll;E. Martínez;M. Santiago‐Raber;H. Amano;Maria Pihlgren;Dragan Marinkovic;S. Izui
一种尚未鉴定的突变，Y连锁自身免疫加速（Yaa），是导致小鼠狼疮样自身免疫综合征加速发展的原因。鉴于Yaa作为BCR信号传导的正调节因子的可能作用，我们探索了Yaa突变的表达是否影响表达4C 8 IgM抗RBC或Sp 6 IgM抗DNA的转基因自身反应性B细胞的发育和活化。在这项研究中，我们表明，Yaa突变的表达诱导4C 8转基因C57 BL/6小鼠的自身免疫性溶血性贫血的致命形式，可能是由于4C 8抗RBC自身反应性B细胞在生命早期的激活。这进一步支持，虽然间接，增加T细胞非依赖性IgM产生的非转基因C57 BL/6小鼠的脾脏轴承Yaa突变。相反，Yaa未能诱导Sp 6抗DNA自身反应性B细胞的活化，这与非转基因C57 BL/6 Yaa小鼠中IgM抗DNA产生缺乏一致。我们的研究结果表明，Yaa可以激活自身反应性B细胞的BCR依赖的方式，有关的差异，在形式和性质的自身抗原。
An as-yet-unidentified mutation, Y-linked autoimmune acceleration (Yaa), is responsible for the accelerated development of lupus-like autoimmune syndrome in mice. In view of a possible role for Yaa as a positive regulator of BCR signaling, we have explored whether the expression of the Yaa mutation affects the development and activation of transgenic autoreactive B cells expressing either 4C8 IgM anti-RBC or Sp6 IgM anti-DNA. In this study, we show that the expression of the Yaa mutation induced a lethal form of autoimmune hemolytic anemia in 4C8 transgenic C57BL/6 mice, likely as a result of activation of 4C8 anti-RBC autoreactive B cells early in life. This was further supported, although indirectly, by increased T cell-independent IgM production in spleens of nontransgenic C57BL/6 mice bearing the Yaa mutation. In contrast, Yaa failed to induce activation of Sp6 anti-DNA autoreactive B cells, consistent with a lack of increased IgM anti-DNA production in nontransgenic C57BL/6 Yaa mice. Our results suggest that Yaa can activate autoreactive B cells in a BCR-dependent manner, related to differences in the form and nature of autoantigens.
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影响因子：
4.4
作者：
Richard R. Hardy;C. Carmack;S. Shinton;R. Riblet;Kyoko Hayakawa
通讯作者：
Richard R. Hardy;C. Carmack;S. Shinton;R. Riblet;Kyoko Hayakawa
影响因子：
4.4
作者：
A. Oliver;F. Martin;J. Kearney
通讯作者：
A. Oliver;F. Martin;J. Kearney
BXSB B 细胞的过度增殖与 Yaa 等位基因有关。
DOI：
10.1006/clin.1996.0170
发表时间：
1996
期刊：
Clinical immunology and immunopathology
影响因子：
--
作者：
DesJardin,LE;Butfiloski,EJ;Sobel,ES;Schiffenbauer,J
通讯作者：
Schiffenbauer,J
影响因子：
4.4
作者：
D. Wofsy
通讯作者：
D. Wofsy
DOI：
10.1073/pnas.98.4.1787
发表时间：
2001-02
影响因子：
11.1
作者：
L. Morel;K. Blenman;B. Croker;E. Wakeland
通讯作者：
L. Morel;K. Blenman;B. Croker;E. Wakeland