StarD5 modulates B cell cholesterol synthesis and IgG1 plasma cell differentiation

StarD5 is an ER stress protein that binds cholesterol and transfers it to the plasma membrane. It additionally binds and regulates 25-hydroxycholesterol (25-HC) levels. However the full function of the StarD5-25-HC axis is unknown. 25-HC has been recently described as an important suppressor of IgA + plasma cell differentiation in the Peyer's patches, and regulates the switch between germinal center and plasma cells. Since StarD5 regulates 25-HC, we examined the role of StarD5 in B cells using StarD5^−/− mice. We found that StarD5^−/− mice have normal B cell development and antibody production at baseline, but after T-dependent immunization a reduction in class-switched IgG1 germinal center B cells and plasma cells was observed. T-independent immune responses additionally result in a reduction in IgG1 responses and this likely B cell intrinsic. In addition, there was impairment at the T1 to T2 transitional B cell stage after T-independent immunization. In conclusion, StarD5 appears important for IgG1 responses in B cells and may regulate B cell development under stress conditions. Our findings suggest a role for StarD5 as a key regulator of B cell function and activation following immunization.