PTPN22 impacts the B cell landscape during chronic virus infection 4379

Abstract Description B cell dysfunction is associated with persistent virus infections. Improving B cell functions, like earlier antibody production or enhanced APC ability, could improve virus clearance. Mice lacking the immune regulatory gene Ptpn22 (PEP-null) clear persistent virus strain LCMV-cl13, whereas wildtype mice (PEP-WT) do not. During autoimmunity, Ptpn22 regulates BCR signaling, affecting activation and differentiation. However, how Ptpn22 impacts B cell dynamics during virus infection remains poorly understood. Based on the findings of Ptpn22 in B cells during autoimmunity, we hypothesize that PEP-null mice will have an altered B cell landscape during virus infection, possibly leading to clearance. First, we profiled B cell subsets in spleen, lymph nodes, and bone marrow from PEP-WT and PEP-null mice at naïve and various days post LCMV-cl13 infection. In naïve splenocytes, PEP-null mice had higher frequency of Follicular and Plasmablasts than PEP-WT. Post infection, PEP-null had less Follicular, but more Plasmablasts compared to PEP-WT in spleen. The inverse was seen in the lymph nodes. In line with this, PEP-null mice had increased serum levels of anti-LCMV IgG2A at 9DPI. Additionally, we determined PEP-null B cells had increased MHC-II but decreased PD-L1 expression in both spleen and lymph nodes. Ongoing studies detail T:B cell interactions that may be regulated by Ptpn22. Results strongly indicate Ptpn22 is a key regulator of B cell dynamics during persistent virus infection. Funding Sources The Madison and Lila Self Graduate Fellowship; CBID CoBRE Research Grant (KU)-P20GM113117* Topic Categories Viral Immunology (VIR)