Lymphotoxin-α-dependent spleen microenvironment supports the generation of memory B cells and is required for their subsequent antigen-induced activation
Lymphotoxin-α-dependent spleen microenvironment supports the generation of memory B cells and is required for their subsequent antigen-induced activation
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DOI：
10.4049/jimmunol.164.5.2508
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发表时间：
2000-03-01
影响因子：
4.4
通讯作者：
Chaplin, DD
中科院分区：
文献类型：
--
作者：
Fu, YX;Huang, GM;Chaplin, DD
淋巴毒素α缺陷型（LTα⁻/⁻）小鼠在初次或二次用绵羊红细胞（SRBC）免疫后，IgG应答显著降低。当将来自SRBC致敏的野生型供体小鼠的脾细胞注入经辐照的未免疫野生型受体小鼠时，它们会产生强烈的记忆性IgG应答，但注入LTα⁻/⁻受体小鼠时则不会，这表明在LTα⁻/⁻小鼠中形成的微环境无法支持这种记忆应答的激活。当用来自致敏的LTα⁻/⁻供体的脾细胞对经辐照的野生型小鼠进行重建，然后用相同的免疫原进行攻击时，未观察到记忆应答，这进一步表明在LTα⁻/⁻环境中无法产生记忆细胞。为了确定LTα⁻/⁻小鼠中哪些淋巴细胞亚群受损，我们使用半抗原/载体系统以及来自不同致敏供体的T细胞和B细胞进行了重建实验。来自LTα⁻/⁻供体的记忆T细胞的产生或表达没有可检测到的缺陷。相反，在LTα⁻/⁻小鼠的微环境中B细胞未被致敏以形成记忆。此外，致敏的野生型记忆B细胞在LTα⁻/⁻微环境中无法表达记忆性IgG应答。因此，脾脏白髓结构（其发育和维持依赖于LTα的表达）对于支持记忆B细胞的产生以及在抗原刺激后允许已有的记忆B细胞表达同种型转换的记忆Ig应答是必需的。
Lymphotoxin alpha-deficient (LT alpha(-/-)) mice show dramatically reduced IgG responses after either primary or secondary immunizations with sheep red brood cells (SRBC), When splenocytes from SRBC-primed wild-type donor mice were infused into irradiated naive wild-type recipient mice, they generated a robust memory IgG response, but not when infused into LT alpha(-/-) recipients, indicating that the microenvironment that develops in LT alpha(-/-) mice is incompetent to support the activation of this memory response. When irradiated wild-type mice were reconstituted with splenocytes from primed LT alpha(-/-) donors and then challenged with the same immunizing Ag, no memory response was observed, indicating further that memory cells could not be generated in the LT alpha(-/-) environment. To address which lymphocyte subsets were impaired in the LT alpha(-/-) mice, we performed reconstitution experiments using a hapten/carrier system and T cells and B cells from different primed donors. There was no detectable defect in either the generation or expression of memory T cells from LT alpha(-/-) donors. In contrast, B cells were not primed for memory in the microenvironment of LT alpha(-/-) mice. Additionally, primed wild-type memory B cells could not express a memory IgG response in the LT alpha(-/-) microenvironment. Thus, splenic white pulp structure, which depends an the expression of LT alpha for its development and maintenance, is needed to support the generation of memory a cells and to permit existing memory B cells to express an isotype switched memory Ig response following antigenic challenge.