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Immunohorizons. 2019 Oct 8;3(10):463-477. doi: 10.4049/immunohorizons.1900048.

Strain-Dependent Contribution of MAVS to Spontaneous Germinal Center Responses.

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Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA 17033.
Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA 17033


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.

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