Metaflammation induced by high caloric intake is  associated to changes in local and systemic B cell immunity. Antibodies play a dual role in metaflammation, high-fat diet (HFD)-induced IgG antibodies contribute to the induction of metaflammation. In contrast, intestinal IgA has been shown to be partly protective, likely by controlling intestinal inflammation and intestinal permeability. Yet, the underlying IgA antibody specificities mediating the protective effects and the role of microbiota remain unclear. In P22 we aim to define the targets and functional role of HFD-induced intestinal IgA antibodies in metaflammation. We therefore measure the HFD-induced secretory IgA (SIgA) reactivities by using single B cell Ig gene sequencing of intestinal plasma, and subsequently identify the SIgA targets by producing large panels of monoclonal antibodies and reactivity testing. Further, by using germ-free animals we define the microbiota-dependent impact of high-fat diet on intestinal B cell immunity. Last, we test a selected set of monoclonal IgA antibodies for their functional effect on metaflammation in vivo using intestinal antibody supplementation in antibody-deficient germ-free mice. P22 may therefore indicate a direct role of HFD-induced antigen-specific IgA antibodies to confer protection against diet-induced metaflammation.

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