Nr4a1 (Nur77) regulates B cell survival and activation. (P1453)

Abstract

Abstract NR4A1 (Nur77) is a member of the NR4A family of orphan nuclear receptors that function as transcription factors. Nur77 is expressed in immune cells, including macrophages, T cells and B cells. However, the role of Nur77 in B cells is not understood. In bone marrow, Nur77 is expressed in early lymphoid precursors and is nearly absent (or maintained at low level) in Pre-pro B cells and in all stages of development through small pre B cells. However, newly formed immature B cells in bone marrow start to express low levels of Nur77 and Nur77 expression increases during transitional stages of B cell development and is maximal in mature B cells in periphery. To investigate the role of Nur77 in B cells, we compared B cell functionalities from normal C57BL/6 and congenic Nur77-deficient mice. We found that Nur77-deficient mice have significantly elevated levels of all four classes of antibodies, which implicates autoimmunity. Nur77-/- mice have 10% more BAFFR+ T1 (transitional stage 1) B cells than WT. Nur77-deficient naïve mice show a 3-fold increase of GL7+ germinal center B cells and a 60% increase of CD38hi memory B cells, compared to those from WT. Those data indicated Nur77-/- mice undergo autoimmunogenic B cells response. In addition, we found that Nur77-/- B cells that are stimulated by anti-IgM and anti-CD40 survived better than WT B cells. Our data suggest that Nur77 plays a primary role in B cell survival and activation.