Increased plasma cell frequency and accumulation of abnormal syndecan-1plus T-cells in Igmu-deficient/lpr mice.
Increased plasma cell frequency and accumulation of abnormal syndecan-1plus T-cells in Igmu-deficient/lpr mice.
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Igmu 缺陷/lpr 小鼠中异常 syndecan-1plus T 细胞的浆细胞频率增加和积累。
作者：
J. Seagal;N. Leider;G. Wildbaum;N. Karin;D. Melamed
MUH链的表达是B细胞发育的重要关卡。在缺乏IgM跨膜尾部外显子的小鼠(MUT小鼠)中，B细胞的发育受阻于前B期。然而，我们发现Fas缺陷的MUMT小鼠(MUMT/LPR)发育出非常少量的同型转换B细胞，并产生高滴度的自身反应性血清抗体。此外，MUMT/LPR小鼠出现严重的淋巴增殖，这两种病理过程都发生在年轻时。这可能表明Fas-Fas配体信号的缺失加剧了B细胞淋巴细胞减少症小鼠的狼疮。为了验证这一点，我们分析了抗体和浆细胞的形成，以及MUMT/LPR小鼠中异常T细胞的积累。我们的结果表明，MUMT/LPR小鼠特别允许抗体产生细胞的发育和积累，从而解释了这些小鼠血清抗体效价高的原因。此外，我们发现MUMT/LPR小鼠的脾和淋巴结中聚集的细胞是表达异常B220+/CD3+表面标志的Alphabeta T细胞，这一表型在其他Fas缺陷小鼠模型中也有描述。引人注目的是，我们发现MUMT/LPR小鼠体内的蓄积细胞表达膜蛋白多糖Syndecan-1，这是一种已知的浆细胞标志物。在缺乏TCRbeta和TCRDelta的小鼠中，这些细胞的发育受阻。我们还发现，MUMT/LPR小鼠的抗体产生和淋巴增殖都受Th1调节。因此，我们的结果表明，在MUMT/LPR小鼠模型中，少量同型转换的B细胞足以启动和繁殖Th1调节的小鼠狼疮。
The expression of muH chain is an important checkpoint in B cell development. In mice deficient for IgM transmembrane tail exons (muMT mice) B cell development is blocked at the pro-B stage. However, we showed that Fas-deficient muMT mice (muMT/lpr) develop a very small population of isotype-switched B cells and produce high titers of self-reactive serum antibodies. In addition, muMT/lpr mice develop severe lymphoproliferation and both pathologic processes occur at young ages. This may suggest that lack of Fas-Fas ligand signaling exacerbates murine lupus in B cell lymphopenic mice. To test this we analyzed antibody and plasma cell formation, and accumulation of abnormal T cells in muMT/lpr mice. Our results show that the muMT/lpr mouse is particularly permissive for the development and accumulation of antibody-producing cells, thereby explaining the high titers of serum antibodies in these mice. In addition, we found that accumulating cells in spleen and lymph nodes of muMT/lpr mice are alphabeta T cells expressing the abnormal B220+/CD3+ surface markers, a phenotype also described for other Fas-deficient mouse models. Strikingly, we found that accumulating cells in muMT/lpr mice express the membrane proteoglycan syndecan-1, a known plasma cell marker. Development of these cells is blocked in mice deficient for TCRbeta and TCRdelta. We also found that both antibody production and lymphoproliferation in muMT/lpr mice are Th1 regulated. Our results, therefore, suggest that in the muMT/lpr mouse model a small population of isotype-switched B cells is sufficient for the initiation and propagation of Th1-regulated murine lupus.
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影响因子：
4.4
作者：
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影响因子：
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DOI：
--
发表时间：
1993
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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Landolfi,MM;VanHouten,N;Russell,JQ;Scollay,R;Parnes,JR;Budd,RC
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DOI：
10.1016/s0074-7696(01)07004-8
发表时间：
2001
期刊：
International review of cytology
影响因子：
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作者：
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DOI：
--
发表时间：
1996
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Rubio,CF;Kench,J;Russell,DM;Yawger,R;Nemazee,D
通讯作者：
Nemazee,D