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Updated: Mar 21, 2026

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
Published on: November 2, 2018
LRRK1 is critical in the regulation of B-cell responses and CARMA1-dependent NF-κB activation
Keiko Morimoto1,2,3, Yoshihiro Baba4,5, Hisaaki Shinohara6
1Department of Immunopathology, World Premier International (WPI) Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
Abstract:
B-cell receptor (BCR) signaling plays a critical role in B-cell activation and humoral immunity. In this study, we discovered a critical function of leucine-rich repeat kinase 1 (LRRK1) in BCR-mediated immune responses. Lrrk1(-/-) mice exhibited altered B1a-cell development and basal immunoglobulin production. In addition, these mice failed to produce IgG3 antibody in response to T cell-independent type 2 antigen due to defects in IgG3 class-switch recombination. Concomitantly, B cells lacking LRRK1 exhibited a profound defect in proliferation and survival upon BCR stimulation, which correlated with impaired BCR-mediated NF-κB activation and reduced expression of NF-κB target genes including Bcl-xL, cyclin D2, and NFATc1/αA. Furthermore, LRRK1 physically interacted and potently synergized with CARMA1 to enhance NF-κB activation. Our results reveal a critical role of LRRK1 in NF-κB signaling in B cells and the humoral immune response.
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