GPR174 signals via Gas to control a CD86-containing gene expression program in B cells [GNAS KO]

GPR174 is abundantly expressed in B and T lymphocytes and has a role in restraining T cell responses, but the function of GPR174 in B cells is less clear. Here we report that upon in vitro culture B cells undergo a spontaneous GPR174-dependent activation process that is associated with marked changes in gene expression, including upregulation of Cd86, Nr4a1, Ccr7 and phosphodiesterases. B cells lacking Gas show a block in induction of the GPR174-dependent program. Spontaneous upregulation of CD86 in cultured B cells is dependent on protein kinase A. Both GPR174- and Gas-deficient B cells show enhanced survival in culture. In vivo, GPR174 contributes to NUR77 expression in follicular B cells and is needed for establishing a marginal zone compartment of normal size. Treatment of mice with lysophosphatidylserine (lysoPS), a GPR174 ligand, is sufficient to promote CD86 upregulation by follicular B cells. These findings demonstrate that GPR174 can signal via Gas to modulate B cell gene expression and show this can occur in vivo in response to lysoPS. Additionally, the findings illuminate a pathway that might be targeted to improve systems for the in vitro study of B cell responses. Overall design: Follicular B cells were isolated from adult mice (N=3 per genotype) for RNA-seq either immediately post-sort or following 1 or 4 hours of culture in complete RPMI 1640 (containing 10% FBS, 10 mM HEPES, 55 µM 2-mercaptoethanol, 2 mM glutamine and 50 IU penicillin/streptomycin)