INDEPENDENT HOMEOSTATIC REGULATION OF B-CELL COMPARTMENTS

In the present study we used mice with a developmental arrest of B cel l production to study the ability of a limited number of normal B cell precursors to populate peripheral B cell pools. In chimeras reconstit uted with mixtures of bone marrow (BM) cells from normal and B cell-de ficient donors, we show that the rate of BM B cell production is a con stant function of the number of BM pre-B cells and is not modified by the peripheral B cell pool size, i.e. there is no feedback regulation of the central pre-B cell compartment by the number of mature B cells. We also show that the physiological number of peripheral B cells requ ires a minimum continuous input of newly formed cells, but is not dete rmined by the number of B cell precursors. Chimeras with a threefold r educed rate of BM B cell production have normal numbers of peripheral B cells. Parabiosis between normal and B cell-deficient mice showed th at the BM B cell production of one mouse suffices to replenish the B c ell pool of three mice. Finally, we show that the compartment of activ ated IgM-secreting B cells is homeostatically autonomous since the num ber of cells it comprises is regulated independently of the size of th e mature B cell pool. The results presented here support a model of th e immune system in which the size of the different B cell compartments , i.e. pre-B, resting B and IgM-secreting, is autonomously regulated.