Alleviation of regulatory B cell exhaustion highlights CpG-B ODN mediated protection from systemic lupus erythematosus 2467

Abstract Description Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is treated through imperfect pharmaceuticals. We have published the protective effects of bacterial DNA (bDNA) on lupus-like disease in MRL/lpr mice. However, bDNA is large, variable, and has potential for off-target effects. CpG-B oligonucleotides (ODNs) are short DNA sequences that mimic bDNA with potentially fewer off-target effects. In this study, MRL/lpr mice were gavaged with CpG-B ODNs, and treated mice had significantly smaller lymph nodes and spleens compared to control mice. In vitro stimulations of MRL/lpr splenocytes with CpG-B ODNs revealed stronger immuno-activation than bDNA. At higher CpG-B ODN concentrations, there were more Ly6C-low monocytes and more IL-10 producing B cells, while at lower CpG-B ODN concentrations, there were more Ly6C-high monocytes and more IL-6 producing B cells, indicating a shift from pro- to anti-inflammatory immune profiles with increasing CpG-B ODN concentrations. Further, there was a positive association of CD38 (an exhaustion marker) with IL-6 production and a negative association with IL-10 production in B cells. These data demonstrate the possible therapeutic potential of CpG-B ODNs while also elucidating a possible mechanism of action by alleviating regulatory B cell exhaustion in a dose-dependent manner. Optimizations of this possible therapeutic will be explored by targeting exhaustion markers to shift towards a more anti-inflammatory immune profile. Topic Categories Basic Autoimmunity (BA)