Follicular B Cells in Thyroids of Mice with Spontaneous Autoimmune Thyroiditis Contribute to Disease Pathogenesis and Are Targets of Anti-CD20 Antibody Therapy
Follicular B Cells in Thyroids of Mice with Spontaneous Autoimmune Thyroiditis Contribute to Disease Pathogenesis and Are Targets of Anti-CD20 Antibody Therapy
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DOI：
10.4049/jimmunol.1301628
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发表时间：
2014-02-01
影响因子：
4.4
通讯作者：
Braley-Mullen, Helen
中科院分区：
文献类型：
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作者：
Hong, So-Hee;Braley-Mullen, Helen
B细胞是NOD.H-2 h4小鼠中自发性自身免疫性甲状腺炎（SAT）发展所必需的，其中它们作为活化CD 4（+）T细胞的重要APC发挥作用。使用抗CD 20耗竭B细胞可有效抑制SAT的发展。本研究的目的是表征SAT中迁移至甲状腺的B细胞，并确定抗CD 20是否有效靶向已建立SAT的小鼠中的这些B细胞。结果表明，SAT小鼠甲状腺浸润B细胞主要为滤泡（FO）B细胞。SAT发生后，FO上CD 80、CD 86和CD 40的表达显著增加，但边缘区、脾B细胞上不显著增加。甲状腺浸润和外周血B细胞的CD 20和CD 24表达低于脾和淋巴结FO B细胞。尽管CD 20表达降低，但抗CD 20在3 d内耗尽了患有SAT的小鼠甲状腺中的大多数B细胞。给予抗CD 20的小鼠甲状腺中的B细胞耗竭比脾脏和淋巴结中的更完全且持续时间更长，并且与血液中的耗竭相当。有效和快速清除甲状腺中的B细胞需要B细胞的循环，因为通过给予FTY 720防止淋巴细胞流出消除了抗CD 20对甲状腺B细胞的作用。因此，B细胞的FO亚群优先促进SAT的发展和持续，并且FO B细胞的抗CD 20靶向有效地消除靶器官中的B细胞，即使甲状腺B细胞具有降低的CD 20表达。
B cells are required for development of spontaneous autoimmune thyroiditis (SAT) in NOD.H-2h4 mice where they function as important APCs for activation of CD4(+) T cells. Depletion of B cells using anti-CD20 effectively inhibits SAT development. The goals of this study were to characterize the B cells that migrate to thyroids in SAT, and to determine whether anti-CD20 effectively targets those B cells in mice with established SAT. The results showed that most thyroid-infiltrating B cells in mice with SAT are follicular (FO) B cells. Expression of CD80, CD86, and CD40 was significantly increased on FO, but not marginal zone, splenic B cells after SAT development. Thyroid-infiltrating and peripheral blood B cells had lower expresion of CD20 and CD24 compared with splenic and lymph node FO B cells. Despite reduced CD20 expression, anti-CD20 depleted most B cells in thyroids of mice with established SAT within 3 d. B cell depletion in thyroids of mice given anti-CD20 was more complete and longer lasting than in spleen and lymph nodes and was comparable to that in blood. Circulation of B cells was required for effective and rapid removal of B cells in thyroids because preventing lymphocyte egress by administration of FTY720 abrogated the effects of anti-CD20 on thyroid B cells. Therefore, the FO subset of B cells preferentially contributes to SAT development and persistence, and anti-CD20 targeting of FO B cells effectively eliminates B cells in the target organ even though thyroid B cells have decreased CD20 expression.