Partial IgA-deficiency with increased Th2-type cytokines in TGF-beta 1 knockout mice.
Partial IgA-deficiency with increased Th2-type cytokines in TGF-beta 1 knockout mice.
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DOI：
10.4049/jimmunol.163.4.1951
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发表时间：
1999-08
影响因子：
4.4
通讯作者：
F. W. Ginkel;S. Wahl;J. Kearney;M. Kweon;K. Fujihashi;P. Burrows;H. Kiyono;J. Mcghee
中科院分区：
文献类型：
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作者：
F. W. Ginkel;S. Wahl;J. Kearney;M. Kweon;K. Fujihashi;P. Burrows;H. Kiyono;J. Mcghee
虽然已经显示TGF-β 1在体外指导B细胞转换为伊加，但是没有研究评估TGF-β 1在体内对粘膜免疫与全身免疫的作用。当分析TGF-β 1基因破坏（TGF-β 1-/-）小鼠的B细胞功能时，观察到血清和外分泌物中伊加水平显著降低，IgG和IgM水平升高。此外，从粘膜和全身淋巴组织中分离的抗体形成细胞（AFC）分析显示IgM、IgG和IgE升高，伊加AFC降低。在TGF-β 1-/-小鼠中观察到IgA定向B细胞的缺乏，尤其是在胃肠道（GI）中。通过TCR触发的脾T细胞表达升高的Th 2型细胞因子，并且与该观察结果一致，在TGF-β 1-/-小鼠中观察到血清IgE增加31倍。因此，不受控制的B细胞应答，包括升高的IgE水平、缺乏伊加和过量的补体结合IgG和IgM Ab，将促进TGF-β 1-/-小鼠粘膜表面的炎症，并可能导致肺部和胃肠道病变，最终导致这些小鼠的早期死亡。
Though it has been shown that TGF-beta 1 directs B cells to switch to IgA in vitro, no studies have assessed TGF-beta 1 effects on mucosal vs systemic immunity in vivo. When the B cell functions of TGF-beta 1 gene-disrupted (TGF-beta 1-/-) mice were analyzed, significantly decreased IgA levels and increased IgG and IgM levels in serum and external secretions were observed. Further, analysis of Ab forming cells (AFC) isolated from both mucosal and systemic lymphoid tissue showed elevated IgM, IgG, and IgE, with decreased IgA AFC. A lack of IgA-committed B cells was seen in TGF-beta 1-/- mice, especially in the gastrointestinal (GI) tract. Splenic T cells triggered via the TCR expressed elevated Th2-type cytokines and, consistent with this observation, a 31-fold increase in serum IgE was seen in TGF-beta 1-/- mice. Thus, uncontrolled B cell responses, which include elevated IgE levels, a lack of antiinflammatory IgA, and an excess of complement-binding IgG and IgM Abs, will promote inflammation at mucosal surfaces in TGF-beta 1-/- mice and likely contribute to pulmonary and GI tract lesions, ultimately leading to the early death of these mice.