B lymphocytes induce the formation of follicular dendritic cell clusters in a lymphotoxin alpha-dependent fashion.
B lymphocytes induce the formation of follicular dendritic cell clusters in a lymphotoxin alpha-dependent fashion.
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DOI：
10.1084/jem.187.7.1009
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发表时间：
1998-04-06
期刊：
影响因子：
--
通讯作者：
Chaplin DD
中科院分区：
文献类型：
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作者：
Fu YX;Huang G;Wang Y;Chaplin DD
淋巴毒素(LT)α由活化的T细胞，尤其是CD_4+T辅助细胞、活化的B细胞和自然杀伤细胞表达，但其在体内的功能尚不完全清楚。我们先前已经证明在LTα缺陷(LTα−/−)小鼠的外周淋巴组织中没有滤泡树突状细胞(FDC)簇和生发中心(GC)。LTα−/−小鼠产生高水平的抗原特异性免疫球蛋白(Ig)M，但用绵羊红细胞免疫后产生的免疫球蛋白水平很低。我们在这里表明，表达LTα的B细胞对于LTα−/−小鼠的初级、继发性和记忆性体液免疫反应的恢复是必不可少的。T细胞不需要表达LTα来支持这些免疫功能。重要的是，表达α的LT B细胞本身是形成功能树突状细胞簇的必要条件和充分条件。一旦这些簇由表达LTα的B细胞形成，那么LTα缺陷的T细胞就可以与B细胞相互作用，产生GC和产生类转换抗体反应。因此，B细胞本身提供了一种基本的信号，诱导和维持对GC形成和类别切换Ig反应至关重要的淋巴微环境。
Lymphotoxin (LT)α is expressed by activated T cells, especially CD4+ T helper type 1 cells, and by activated B and natural killer cells, but the functions of this molecule in vivo are incompletely defined. We have previously shown that follicular dendritic cell (FDC) clusters and germinal centers (GCs) are absent from the peripheral lymphoid tissues of LTα-deficient (LTα−/−) mice. LTα−/− mice produce high levels of antigen-specific immunoglobulin (Ig)M, but very low levels of IgG after immunization with sheep red blood cells. We show here that LTα-expressing B cells are essential for the recovery of primary, secondary, and memory humoral immune responses in LTα−/− mice. It is not necessary for T cells to express LTα to support these immune functions. Importantly, LTα-expressing B cells alone are essential and sufficient for the formation of FDC clusters. Once these clusters are formed by LTα-expressing B cells, then LTα-deficient T cells can interact with B cells to generate GCs and productive class-switched antibody responses. Thus, B cells themselves provide an essential signal that induces and maintains the lymphoid microenvironment essential for GC formation and class-switched Ig responses.