We demonstrate that adoptive transfer of peritoneal cavity B cells fails to replenish the peripheral B-1 cells in adult B cell-deficient (μ^−/−) mice but does replenish adult RAG-1^−/− mice. We show that this lack of self-replenishment in μ^−/− mice is mediated by strongly inhibitory, radiation-sensitive CD4⁺ T cells that also function in cotransfer studies to block the reconstitution of B-1 cells and inhibit accumulation of bone marrow-derived B-2 cells in the periphery in irradiated recipients. CD8⁺ T cells from μ^−/− do not mediate this inhibition. The inhibitory CD4⁺ T cells develop early in life, because B-1 cell replenishment occurs normally when B-1 cells are transferred into μ^−/− neonates. Thus, we conclude that the presence of B cells in the neonate conditions the CD4⁺ T-cell population to permit the establishment and maintenance of normal B cell pools throughout life.