Plexin-D1 Is a Novel Regulator of Germinal Centers and Humoral Immune Responses
Plexin-D1 Is a Novel Regulator of Germinal Centers and Humoral Immune Responses
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DOI：
10.4049/jimmunol.1003464
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发表时间：
2011-05-15
影响因子：
4.4
通讯作者：
Ting, Jenny P. -Y.
中科院分区：
文献类型：
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作者：
Holl, Eda K.;O'Connor, Brian P.;Ting, Jenny P. -Y.
长寿体液免疫反应依赖于生发中心(GC)反应中记忆B细胞和长寿浆细胞的产生。这些以类别切换的免疫球蛋白和高亲和力抗体为特征的记忆隔间是成功接种疫苗的基础。我们报道了Plexin家族的一个新成员，Plexin-D1，控制GC反应，是二次体液免疫反应所必需的。B细胞的成熟、边缘带前体的发育、暗带和亮带的形成、Ig lambda(+)和Ig kappa(+)B细胞的偏斜、B1/B2的发育和初始的卵泡外反应都不需要Plexin-D1。随着B细胞的激活，Plexin-D1的表达增加，PlxnD1(-/-)小鼠在T依赖的免疫激活过程中出现GC反应缺陷。PlxnD1(-/-)B细胞向GC趋化因子CXCL12、CXCL13和CCL19迁移存在缺陷。因此，PlxnD1(-/-)小鼠表现出IgG1和IgG2b产生缺陷，但没有IgG3血清抗体，伴随着长期存活的骨髓浆细胞减少和回忆体液记忆反应。这些数据表明，免疫网络蛋白在GC反应和免疫记忆生成中发挥了新的作用。免疫学杂志，2011,186：5603-5611。
Long-lived humoral immune responses depend upon the generation of memory B cells and long-lived plasma cells during the germinal center (GC) reaction. These memory compartments, characterized by class-switched IgG and high-affinity Abs, are the basis for successful vaccination. We report that a new member of the plexin family of molecules, plexin-D1, controls the GC reaction and is required for secondary humoral immune responses. Plexin-D1 was not required for B cell maturation, marginal zone precursor development, dark and light zone formation, Ig lambda(+) and Ig kappa(+) B cell skewing, B1/B2 development, and the initial extrafollicular response. Plexin-D1 expression was increased following B cell activation, and PlxnD1(-/-) mice exhibited defective GC reactions during T-dependent immune activation. PlxnD1(-/-) B cells showed a defect in migration toward the GC chemokines, CXCL12, CXCL13, and CCL19. Accordingly, PlxnD1(-/-) mice exhibited defective production of IgG1 and IgG2b, but not IgG3 serum Ab, accompanied by reductions in long-lived bone marrow plasmacytes and recall humoral memory responses. These data show a new role for immune plexins in the GC reaction and generation of immunologic memory. The Journal of Immunology, 2011, 186: 5603-5611.