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CD11c+ autoimmune-associated B cells have an increased phagocytosis activity and T cell activation which is regulated by metabolic intervention in lupus mice

ABSTRACT: Specific metabolic program is required for generation of immune cells and their proper function. Since the description of age-associated or autoimmune-associated B cells (ABCs), there has been a growing interest in the role of these cells in autoimmunity. ABCs have many distinct functional properties, including antigen presentation to T cells and autoantibody production in lupus mouse models. Metabolic properties which support these functions are unknown in ABCs. In this study, we showed that ABCs are metabolically hyperactivated than follicular (FO) B cells. There was an increased glycolysis and oxidative phosphorylation (OXPHOS) in ABCs. In line with this observation, ABCs express key costimulatory molecules for T cell activation with distinct group of cytokines. T cell proliferation and activation were induced by both FO B and ABCs in antigen-dependent manner. However, ABCs induce stronger T cell receptor signaling from naïve CD4+ T cells, leading to differentiation of follicular helper T (Tfh) cells. ABCs actively internalize OVA protein and increased autophagy formation. Treatment of ABCs with metformin suppressed antigen presentation by decreasing antigen uptake, leading to a defective generation of Tfh cells. Taken together, these findings reveal distinct metabolic activity in ABCs and define fundamental connection between metabolism and function within ABCs.

ORGANISM(S): Mus musculus

PROVIDER: GSE214185 | GEO | 2023/09/06

REPOSITORIES: GEO

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