LRRK2 affects cytokine production and Ig secretion in activated B cells (P1060)

Abstract

Abstract Leucine-rich repeat kinase 2 (LRRK2), a 286 KDa multi-domain protein, is strongly associated with familial Parkinson disease, Crone’s disease, as well as Lupus in GWAS studies. However, the pathogenic mechanisms of LRRK2 are still unclear. In order to further study its functions, we developed a strain of GFP knockin knockout (KIKO) mice that replaced the exon2 of lrrk2 gene with gfp and eliminated endogenous LRRK2. Since it is highly expressed in different immune cells, especially B cells, we first determined that LRRK2 mainly expressed in T2, follicular, and marginal zone B cells, but not in pro-, pre-, immature, T1 or B1 B cells. After B cell activation by LPS or anti-IgM/ anti-CD40, there was no difference in proliferation as well as apoptosis between Wt and KIKO B cells. However, Wt and KIKO B cells showed statistically significant differences in cytokine production profiles. Re-stimulation of activated B cells by PMA and ionomycin showed KIKO B cells has differential cytokine productions. Meanwhile, activated KIKO B cells also showed impaired IgA and IgG3 secretion, though the Ig switching was normal. These indicate that LRRK2 may have a role in B cell effector functions, and further investigation is needed.