Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, New York 11794, USA.
FASEB J. 2011 May;25(5):1680-96. doi: 10.1096/fj.10-174656. Epub 2011 Feb 9.
We investigated the hypothesis that salivary gland inoculation stimulates formation of ectopic germinal centers (GCs), transforming the gland into a mucosal inductive site. Intraglandular infection of mice with murine cytomegalovirus (MCMV; control: UV-inactivated MCMV) induces salivary gland ectopic follicles comprising cognate interactions between CD4(+) and B220(+) lymphocytes, IgM(+) and isotype-switched IgG(+) and IgA(+) B cells, antigen presenting cells, and follicular dendritic cells. B cells coexpressed the GC markers GCT (57%) and GL7 (52%), and bound the lectin peanut agglutinin. Lymphoid follicles were characterized by a 2- to 3-fold increase in mRNA for CXCL13 (lymphoid neogenesis), syndecan-1 (plasma cells), Blimp-1 (plasma cell development/differentiation), and a 2- to 6-fold increase for activation-induced cytidine deaminase, PAX5, and the nonexcised rearranged DNA of an IgA class-switch event, supporting somatic hypermutation and class-switch recombination within the salivary follicles. Intraglandular inoculation also provided protection against a systemic MCMV challenge, as evidenced by decreased viral titers (10(5) plaque-forming units to undetectable), and restoration of normal salivary flow rates from a 6-fold decrease. Therefore, these features suggest that the salivary gland participates in oral mucosal immunity via generation of ectopic GCs, which function as ectopic mucosal inductive sites.
我们研究了唾液腺接种刺激异位生发中心（GC）形成的假说，将腺体转化为黏膜诱导部位。用鼠巨细胞病毒（MCMV；对照：UV 灭活的 MCMV）对小鼠进行腺内感染，诱导唾液腺异位滤泡形成，包括 CD4（+）和 B220（+）淋巴细胞、IgM（+）和同种型转换的 IgG（+）和 IgA（+）B 细胞、抗原呈递细胞和滤泡树突状细胞之间的同源相互作用。B 细胞共表达 GC 标记物 GCT（57%）和 GL7（52%），并结合花生凝集素。淋巴细胞滤泡的特征是 CXCL13（淋巴生成）、 syndecan-1（浆细胞）、Blimp-1（浆细胞发育/分化）的 mRNA 增加 2-3 倍，激活诱导的胞嘧啶脱氨酶、PAX5 和未切除的 IgA 类转换事件的重排 DNA 增加 2-6 倍，支持唾液滤泡中的体细胞超突变和类别转换重组。腺内接种还提供了针对系统性 MCMV 挑战的保护，如病毒滴度降低（10（5）噬菌斑形成单位至无法检测），以及正常唾液流速从 6 倍下降恢复正常。因此，这些特征表明唾液腺通过产生异位 GC 参与口腔黏膜免疫，GC 作为异位黏膜诱导部位发挥作用。
