A proposed model for the function of the TNF-α/IGFBP-1/IGF-1 axis in regulating B-cell lymphopoiesis in aging. B-cell lymphocyte production in the BM is regulated in aging by the level of IGF-1 in the circulation. The long-lived B cells, which accumulate in the periphery with aging, produce large amounts of the pro-inflammatory cytokine TNF-α, which stimulates the liver to increase production of IGFBP-1. The increased IGFBP-1 binds IGF-1 and sequesters its activity in the BM, resulting in a suppressed B-cell lymphopoiesis. Upon B-cell depletion, the peripheral compartment is replenished with newly generated naïve B cells that secrete small amounts of TNF-α, resulting in a decline in the plasma level of TNF-α. The reduced TNF-α is followed by a decrease in IGFBP-1 and a consequential increase in IGF-1 and reactivation of B-cell lymphopoiesis in the BM.