Figure 4.

NF-κB in lymphopoiesis. NF-κB plays a pro-survival role in common lymphoid precursor (CLP) cells which give rise to B- and T-cell lineages. B-cell development occurs in the bone marrow, where NF-κB protects pre-B cells from pro-apoptotic stimuli including TNFα. Signaling to NF-κB through the pre-B cell receptor mediates survival of Pre-B cells, which then undergo light chain recombination to produce a functional B cell receptor. NF-κB provides a necessary pro-survival signal during Igλ but not Igκ rearrangement. Expression of BCR leads to NF-κB-dependent differentiation into immature B cells. High levels of BCR signaling, i.e., through recognition of self-antigen, results in negative selection through the loss of NF-κB activity. Transitional B cells exit the bone marrow and migrate to the spleen, where they mature and differentiate, a process that also requires NF-κB. T-cell development occurs following migration of precursor cells into the thymus. Stimulation of NF-κB through pre-TCRα provides a pro-survival signal allowing recombination of the TCR α chain and maturation to the double-positive (DP) stage. Optimal signaling through the TCRα/β complex induces NF-κB-dependent survival pathways, while a failure to signal or high level signaling results in death by neglect or negative selection, respectively. Intermediate high NF-κB activation facilitates intrathymic regulatory T cell (Treg) development. NF-κB activity is required for the maintenance of long-lived B and T cells. (CLP, common lymphoid progenitor; ETP, early thymic progenitor; DN, double negative – CD4⁻CD8⁻; DP, double positive – CD4⁺CD8⁺; SP, single positive – either CD4⁺CD8⁻ or CD4⁻CD8⁺)