UC San Diego

B cells are an important facet of the immune response against chronic viral infection. In the first chapter of this thesis, we studied the role of gut microbiome composition on B cell responses to chronic lymphocytic choriomeningitis virus clone 13 (LCMV Cl13) infection in mice. We used genetically similar mice from two different vendors, Taconic Biosciences and The Jackson Laboratory, that have been established to contain dramatically different intestinal microbiome compositions. We found that mice from Taconic Biosciences differed from mice from The Jackson Laboratory in the accumulation of B cells in the blood and spleen at certain timepoints during persistent LCMV Cl13 infection. Co-housing mice from different vendors resulted in the partial transfer of B cell accumulation in the blood and spleen and also resulted in impaired viral clearance. In the second chapter, we investigated the role of late B cell-derived IL-27 on B cell responses to persistent LCMV infection in mice. We used genetic systems to modulate the availability of the IL-27p28 subunit in an inducible manner specifically in B cells. Late deletion of B cell-derived IL-27p28 resulted in subtle increases in the accumulation of IgD-IgM+ non-naïve B cells and IgD-IgM- class-switched B cells, which peaked by 60 days post-infection. At even later timepoints post-infection, B cell-derived IL-27p28 deletion resulted in increases in the accumulation of total B cells. Overall, our results suggest that B cell responses to persistent viral infection are modulated by gut microbiome composition and may be downregulated by B cell-derived IL-27.