CD4+ T cells derived from B cell-deficient mice inhibit the establishment of peripheral B cell pools

We demonstrate that adoptive transfer of peritoneal cavity B cells fails to replenish the peripheral B-1 cells in adult B cell-deficient (mu(-/-)) mice but does replenish adult RAG-1(-/-) mice. We show that this lack of self-replenishment in mu(-/-) 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 mu(-/-) 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 mu(-/-) 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.