Finke D, Baribaud F, Diggelmann H, Acha-Orbea H
Ludwig Institute for Cancer Research, Lausanne Branch, and Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
J Immunol. 2001 May 15;166(10):6266-75. doi: 10.4049/jimmunol.166.10.6266.
B cells can either differentiate in germinal centers or in extrafollicular compartments of secondary lymphoid organs. Here we show the migration properties of B cells after differentiation in murine peripheral lymph node infected with mouse mammary tumor virus. Naive B cells become activated, infected, and carry integrated retroviral DNA sequences. After production of a retroviral superantigen, the infected B cells receive cognate T cell help and differentiate along the two main differentiation pathways analogous to classical Ag responses. The extrafollicular differentiation peaks on day 6 of mouse mammary tumor virus infection, and the follicular one becomes detectable after day 10. B cells participating in this immune response carry a retroviral DNA marker that can be detected by using semiquantitative PCR. We determined the migration patterns of B cells having taken part in the T cell-B cell interaction from the draining lymph node to different tissues. Waves of immigration and retention of infected cells in secondary lymphoid organs, mammary gland, salivary gland, skin, lung, and liver were observed correlating with the two peaks of B cell differentiation in the draining lymph node. Other organs revealed immigration of infected cells at later time points. The migration properties were correlated with a strong up-regulation of alpha(4)beta(1) integrin expression. These results show the migration properties of B cells during an immune response and demonstrate that a large proportion of extrafolliculary differentiating plasmablasts can escape local cell death and carry the retroviral infection to peripheral organs.
B细胞可在生发中心或二级淋巴器官的滤泡外区域分化。在此,我们展示了在感染小鼠乳腺肿瘤病毒的小鼠外周淋巴结中分化后的B细胞的迁移特性。初始B细胞被激活、感染,并携带整合的逆转录病毒DNA序列。在产生逆转录病毒超抗原后,受感染的B细胞获得同源T细胞的辅助,并沿着类似于经典抗原应答的两条主要分化途径进行分化。在小鼠乳腺肿瘤病毒感染的第6天,滤泡外分化达到峰值,而滤泡内分化在第10天后可检测到。参与这种免疫反应的B细胞携带一种逆转录病毒DNA标记物,可通过半定量PCR检测到。我们确定了参与T细胞 - B细胞相互作用的B细胞从引流淋巴结到不同组织的迁移模式。观察到感染细胞在二级淋巴器官、乳腺、唾液腺、皮肤、肺和肝脏中的迁移和滞留波,这与引流淋巴结中B细胞分化的两个峰值相关。其他器官在较晚时间点显示出感染细胞的迁移。迁移特性与α(4)β(1)整合素表达的强烈上调相关。这些结果显示了免疫反应期间B细胞的迁移特性,并证明大部分滤泡外分化的浆母细胞能够逃避局部细胞死亡,并将逆转录病毒感染传播到外周器官。