Lrba^-/- murine B cells show NF-κB overactivation and altered BCR signaling.

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B742
Abstract ID: 5085

Presenting Author:
Daniela Pérez-Pérez , PhD student at Univ. Nacional Autónoma de México, Inst. Nacional de Pediatría

Abstract:

Lipopolysaccharide-Responsive Beige-like anchor (LRBA) is a scaffolding protein whose deficiency is associated with an inborn error of immunity error like common variable immunodeficiency. Patients with LRBA deficiency have a heterogeneous clinical presentation including hypogammaglobulinemia, reduction of B and T regulatory cells, recurrent infections, and autoimmune diseases. Functions of Lrba on T regulatory cells have been described, however, function on B cells remains unknown. This work aims to identify the function of Lrba in B-cell receptor (BCR) signaling.

Lrba-deficient mice (Lrba^-/-) have a higher number of Transitional 1 B cells in the spleen. Flow cytometry assays showed reduced B cell proliferation and an increased cell death, in response to B-cell Receptor (BCR) crosslinking. Immunoblot and confocal microscopy revealed an increased activation of p50, p65, and IκBα (components of the canonical pathway of NF-κB) in Lrba^-/- B cells under basal conditions with a subsequent reduced response after BCR crosslinking. Co-immunoprecipitation assays suggest an interaction between Lrba and components of BCR signaling such as PLC-γ2 and p65.

The activated phenotype of Lrba^-/- B cells as well as the interaction with p65 and PLC-γ2 indicates that Lrba is involved in the regulation of NF-κB activation driven by BCR signaling, which finally impacts on survival of B cells.