NONO regulates B-cell development and B-cell receptor signaling.

The paraspeckle protein NONO is a multifunctional nuclear protein participating in the regulation of transcriptional regulation, mRNA splicing and DNA repair. However, whether NONO plays a role in lymphopoiesis is not known. In this study, we generated mice with global deletion of NONO and bone marrow (BM) chimeric mice in which NONO is deleted in all of mature B cells. We found that the global deletion of NONO in mice did not affect T-cell development but impaired early B-cell development in BM at pro- to pre-B-cell transition stage and B-cell maturation in the spleen. Studies of BM chimeric mice demonstrated that the impaired B-cell development in NONO-deficient mice is B-cell-intrinsic. NONO-deficient B cells displayed normal BCR-induced cell proliferation but increased BCR-induced cell apoptosis. Moreover, we found that NONO deficiency impaired BCR-induced activation of ERK, AKT, and NF-κB pathways in B cells, and altered BCR-induced gene expression profile. Thus, NONO plays a critical role in B-cell development and BCR-induced B-cell activation.