Cell-Autonomous Role for NF-κB in Immature Bone Marrow B Cells

The NF-kappa B transcription factors have many essential functions in B cells, such as during differentiation and proliferation of Ag-challenged mature B cells, but also during final maturation of developing B cells in the spleen. Among the various specific functions NF-kappa B factors carry out in these biologic contexts, their ability to assure the survival of mature and maturing B cells in the periphery stands out. Less clear is what if any roles NF-kappa B factors play during earlier stages of B cell development in the bone marrow. Using mice deficient in both NF-kappa B1 and NF-kappa B2, which are thus partially compromised in both the classical and alternative activation pathways, we demonstrate a B cell-autonomous contribution of NF-kappa B to the survival of immature B cells in the bone marrow. NF-kappa B1 and NF-kappa B2 also play a role during the earlier transition from proB to late preB cells; however, in this context these factors do not act in a B cell-autonomous fashion. Although NF-kappa B1 and NF-kappa B2 are not absolutely required for survival and progression of immature B cells in the bone marrow, they nevertheless make a significant contribution that marks the beginning of the profound cell-autonomous control these factors exert during all subsequent stages of B cell development. Therefore, the lifelong dependency of B cells on NF-kappa B-mediated survival functions is set in motion at the time of first expression of a full BCR. The Journal of Immunology, 2009, 182: 3406-3413.