Itakura Atsuko, Szczepanik Marian, Campos Regis A, Paliwal Vipin, Majewska Monika, Matsuda Hiroshi, Takatsu Kiyoshi, Askenase Philip W
Section of Allergy and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8013, USA.
J Immunol. 2005 Dec 1;175(11):7170-8. doi: 10.4049/jimmunol.175.11.7170.
Elicitation of contact sensitivity (CS), a classic example of T cell-mediated immunity, requires Ag-specific IgM Abs to trigger an initiation process. This early process leads to local recruitment of CS-effector T cells after secondary Ag challenge. These Abs are produced by the B-1 subset of B cells within 1 day after primary skin immunization. In this study we report the surprising observation that B-1 cells in the peritoneal cavity are activated as early as 1 h after naive mice are painted with a contact-sensitizing Ag on the skin of the trunk and feet to begin the initiation of CS. B-1 cells in the spleen and draining lymph nodes produce the initiating Abs by 1 day after immunization, when we found increased numbers of Ag-specific IgM Ab-producing cells in these tissues by ELISPOT assay. Importantly, we show that contact-activated peritoneal B-1 cells migrate to these lymphoid tissues and then differentiate into Ag-specific IgM Ab-producing cells, resulting in specific CS-initiating IgM Abs in the serum by 1 day. Furthermore, pertussis toxin, which is known to inhibit signaling via G protein-coupled chemokines, inhibited the migration of contact-activated peritoneal B-1 cells to the lymphoid tissues, probably due to BLR-1 (Burkitt lymphoma receptor-1). These findings indicate that within 1 h after contact skin immunization, B-1 cells in the peritoneal cavity are activated to migrate to the lymphoid tissues by chemokine-dependent mechanisms to produce serum Ag-specific IgM Abs within 1 day after immunization, leading to local recruitment of CS-effector T cells.
接触敏感性(CS)的激发是T细胞介导免疫的经典例子,需要抗原特异性IgM抗体来触发起始过程。这个早期过程会导致在再次接触抗原后局部募集CS效应T细胞。这些抗体是在初次皮肤免疫后1天内由B细胞的B-1亚群产生的。在本研究中,我们报告了一个惊人的发现:在用接触致敏抗原涂抹在新生小鼠躯干和足部皮肤后,腹腔内的B-1细胞早在1小时后就被激活,从而开始CS的起始过程。免疫后1天,脾脏和引流淋巴结中的B-1细胞产生起始抗体,此时我们通过ELISPOT分析发现这些组织中产生抗原特异性IgM抗体的细胞数量增加。重要的是,我们表明接触激活的腹腔B-1细胞迁移到这些淋巴组织,然后分化为产生抗原特异性IgM抗体的细胞,导致血清中在1天时出现特异性CS起始IgM抗体。此外,已知抑制通过G蛋白偶联趋化因子信号传导的百日咳毒素抑制了接触激活的腹腔B-1细胞向淋巴组织的迁移,这可能是由于BLR-1(伯基特淋巴瘤受体-1)。这些发现表明,在接触皮肤免疫后1小时内,腹腔内的B-1细胞被激活,通过趋化因子依赖机制迁移到淋巴组织,在免疫后1天内产生血清抗原特异性IgM抗体,从而导致CS效应T细胞的局部募集。