LRRK1 is critical in the regulation of B-cell responses and CARMA1-dependent NF-κB activation

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 NarazakiTomohiro Kurosaki, Toshihiko Toyofuku, Atsushi Kumanogoh

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


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-x L, 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.

Original languageEnglish
Article number25738
JournalScientific reports
Publication statusPublished - May 11 2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General


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