Strain-Dependent Contribution of MAVS to Spontaneous Germinal Center Responses
| Autor: | Adam J. Fike, Sathi Babu Chodisetti, Nicholas M Choi, Stephanie L. Schell, Zia Ur Rahman, Kristen N. Bricker |
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| Rok vydání: | 2019 |
| Předmět: |
Agonist
medicine.drug_class Immunology Spleen Biology medicine.disease_cause Autoimmunity Adjuvants Immunologic Species Specificity medicine Animals Immunology and Allergy Follicular B cell B cell Adaptor Proteins Signal Transducing Mice Knockout B-Lymphocytes Imiquimod Membrane Glycoproteins RNA Germinal center General Medicine TLR7 Germinal Center medicine.anatomical_structure Toll-Like Receptor 7 Genetic Background |
| Zdroj: | ImmunoHorizons. 3:463-477 |
| ISSN: | 2573-7732 |
| Popis: | Germinal centers (GCs) are essential for the production of somatically hypermutated, class-switched Abs that are protective against infection, but they also form in the absence of purposeful immunization or infection, and are termed spontaneous GCs (Spt-GCs). Although Spt-GCs can arise in nonautoimmune-prone mice, aberrant regulation of Spt-GCs in autoimmune-prone mice is strongly associated with the development of autoimmune diseases like systemic lupus erythematosus. The formation of Spt-GCs is crucially driven by TLR7-mediated RNA sensing. However, the impact of MAVS-dependent, Rig-like receptor–mediated RNA sensing on the Spt-GC response remains unknown. In this study, we assessed the Spt-GC response and splenic B cell development in two MAVS-deficient mice with distinct genetic backgrounds. Importantly, we found that MAVS differentially controls Spt-GC responses and B cell development, depending on genetic background. B6/129 mixed background MAVSKO mice had nearly absent Spt-GC responses in the spleen and cervical lymph nodes, which were associated with impaired splenic B cell development, in addition to impaired B cell activation and TLR7 expression. Interestingly, treatment of mice with TLR7 agonist could partially rescue GC responses by overcoming follicular B cell activation deficits. Contrastingly, the absence of MAVS on a B6 background resulted in normal B cell development and Spt-GC formation. Our results highlight important differences in the contribution of MAVS to B cell development and Spt-GC function, depending on the genetic background, warranting greater regard for the impact of genetic background in further studies using these mice for the study of autoimmunity. |
| Databáze: | OpenAIRE |
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