B-1 and B-2 cell-derived immunoglobulin M antibodies are nonredundant components of the protective response to influenza virus infection.
B-1 and B-2 cell-derived immunoglobulin M antibodies are nonredundant components of the protective response to influenza virus infection.
复制标题
DOI：
10.1084/jem.192.2.271
复制
发表时间：
2000-07-17
影响因子：
15.3
通讯作者：
Chen, J
中科院分区：
文献类型：
--
作者：
Baumgarth, N;Herman, O C;Jager, G C;Brown, L E;Herzenberg, L A;Chen, J
我们研究了分泌型免疫球蛋白 (Ig)M 在防止流感病毒感染方面的作用，并描述了 B-1 与 B-2 细胞来源的 IgM 在此过程中的相对贡献。与野生型对照相比，缺乏分泌型 IgM 但能够表达表面 IgM 并分泌其他 Ig 类别的小鼠显示出病毒清除率和存活率显着降低。仅 B-1 或 B-2 细胞缺乏分泌 IgM 能力的辐射嵌合体显示出与 B-1 和 B-2 细胞均不分泌 IgM 的小鼠相似的死亡率。同种异型嵌合体的发现部分解释了生存对两种 IgM 来源的依赖，即感染前存在广泛交叉反应的 B-1 细胞衍生的天然 IgM，而病毒株特异性的 B-2 细胞衍生的 IgM 仅在感染后出现。此外，一种或两种来源分泌的 IgM 缺乏会显着损害抗病毒 IgG 反应。仅用未感染小鼠的含 IgM 血清重建缺乏 B-1 细胞衍生 IgM 的嵌合体，可提高存活率和病毒特异性 IgG 的血清水平。因此，病毒诱导的 IgM 必须在天然 IgM 存在的情况下分泌，以有效诱导特异性 IgG 和免疫保护，将 B-1 和 B-2 细胞衍生的 IgM 抗体识别为抗病毒反应的非冗余成分。
We have studied the role of secreted immunoglobulin (Ig)M in protection from infection with influenza virus and delineated the relative contributions of B-1 versus B-2 cell–derived IgM in this process. Mice deficient in secreted IgM but capable of expressing surface IgM and secreting other Ig classes show significantly reduced virus clearance and survival rates compared with wild-type controls. Irradiation chimeras in which only either B-1 or B-2 cells lack the ability to secrete IgM show mortality rates similar to those of mice in which neither B-1 nor B-2 cells secrete IgM. Dependence on both sources of IgM for survival is partially explained by findings in allotype chimeras that broadly cross-reactive B-1 cell–derived natural IgM is present before infection, whereas virus strain–specific, B-2 cell–derived IgM appears only after infection. Furthermore, lack of IgM secreted from one or both sources significantly impairs the antiviral IgG response. Reconstitution of chimeras lacking B-1 cell–derived IgM only with IgM-containing serum from noninfected mice improved both survival rates and serum levels of virus-specific IgG. Thus, virus-induced IgM must be secreted in the presence of natural IgM for efficient induction of specific IgG and for immune protection, identifying B-1 and B-2 cell–derived IgM antibodies as nonredundant components of the antiviral response.