Strain-Dependent Contribution of MAVS to Spontaneous Germinal Center Responses

• Published in: ImmunoHorizons 2019-10, Vol.3 (10), p.463-477
• Main Authors: Schell, Stephanie L, Chodisetti, Sathi Babu, Fike, Adam J, Choi, Nicholas M, Bricker, Kristen N, Rahman, Ziaur S M
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - immunology; Adjuvants, Immunologic - pharmacology; Animals; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; Genetic Background; Germinal Center - immunology; Imiquimod - pharmacology; Membrane Glycoproteins - immunology; Mice, Knockout; Species Specificity; Spleen - cytology; Toll-Like Receptor 7 - immunology
• ISSN: 2573-7732; 2573-7732
• DOI: 10.4049/immunohorizons.1900048

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.