Strain-Dependent Contribution of MAVS to Spontaneous Germinal Center Responses

Stephanie L. Schell, Sathi Babu Chodisetti, Adam J. Fike, Nicholas M. Choi, Kristen N. Bricker, Ziaur S.M. Rahman

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)463-477
Number of pages15
JournalImmunoHorizons
Volume3
Issue number10
DOIs
StatePublished - Oct 1 2019

All Science Journal Classification (ASJC) codes

  • Immunology
  • Immunology and Allergy

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