B-cell anergy induces a Th17 shift in a novel B lymphocyte transgenic NOD mouse model, the 116C-NOD mouse
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- 作者：Jorge Carrascal ; Jorge Carrillo ; Berta Arpa ; Leire Egia-Mendikute ; Estela Rosell-Mases ; Irma Pujol-Autonell ; Raquel Planas ; Conchi Mora ; Dí ; dac Mauricio ; Rosa Maria Ampudia ; Marta Vives-Pi and Joan Verdaguer
- 关键词：B lymphocyte ; Immune tolerance ; NOD mouse ; Th17 ; Transgenic ; Type 1 diabetes
- 刊名：European Journal of Immunology
- 出版年：2016
- 出版时间：March 2016
- 年：2016
- 卷：46
- 期：3
- 页码：593-608
- 全文大小：1851K
- ISSN：1521-4141
文摘
Autoreactive B lymphocytes play a key role as APCs in diaebetogenesis. However, it remains unclear whether B-cell tolerance is compromised in NOD mice. Here, we describe a new B lymphocyte transgenic NOD mouse model, the 116C-NOD mouse, where the transgenes derive from an islet-infiltrating B lymphocyte of a (8.3-NODxNOR) F1 mouse. The 116C-NOD mouse produces clonal B lymphocytes with pancreatic islet beta cell specificity. The incidence of T1D in 116C-NOD mice is decreased in both genders when compared with NOD mice. Moreover, several immune selection mechanisms (including clonal deletion and anergy) acting on the development, phenotype, and function of autoreactive B lymphocytes during T1D development have been identified in the 116C-NOD mouse. Surprisingly, a more accurate analysis revealed that, despite their anergic phenotype, 116C B cells express some costimulatory molecules after activation, and induce a T-cell shift toward a Th17 phenotype. Furthermore, this shift on T lymphocytes seems to occur not only when both T and B cells contact, but also when helper T (Th) lineage is established. The 116C-NOD mouse model could be useful to elucidate the mechanisms involved in the generation of Th-cell lineages.