LRRK1 is Critical in the Regulation of B-cell Responses and CARMA1-dependent NF-κB Activation

Overview

Journal Sci Rep

Specialty Science

Date 2016 May 12

PMID 27166870

Citations 13

Authors

Keiko Morimoto

Yoshihiro Baba

Hisaaki Shinohara

Sujin Kang

Satoshi Nojima

Tetsuya Kimura

Daisuke Ito

Yuji Yoshida

Yohei Maeda

Hana Sarashina-Kida

Masayuki Nishide

Takashi Hosokawa

Yasuhiro Kato

Yoshitomo Hayama

Yuhei Kinehara

Tatsusada Okuno

Hyota Takamatsu

Toru Hirano

Yoshihito Shima

Masashi Narazaki

Tomohiro Kurosaki

Toshihiko Toyofuku

Atsushi Kumanogoh

Affiliations

Soon will be listed here.

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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