Precursors of Murine B Lymphocytes

The precursors of B lymphocytes have previously been distinguished and characterized by various parameters including their ability to generate B cells after adoptive transfer, expression of surface markers a n d / o r B cell function after short-term induction in vitro, and their synthesis but not surface display o f immunoglobu l in (Ig) heavy chains (1-19). The extent to which these cells are heterogenous in fetal and adult life is not known, and it is also not clear to what extent their numbers depend on differentiation from muhipotent ia l hemopoietic stem cells. The ability to form foci of proliferating hemopoiet ic cells in spleens of irradiated recipients is usually ascribed to uncommit ted colony-forming stem cells (CFU-s) 1 but recent studies suggest that differentiation options for some CFU-s may be restricted (20). O u r previous studies identified one or more cell types which were capable of restoring colony-forming B cells (CFU-B) to partially immunodeficient C B A / N mice (6, 19). These ceils were neither surface Ig ÷ (B cells) nor closely related to CFU-s. Tha t is, the restorative capacity of various cell supensions did not correlate with numbers of either CFU-s or lymphocytes, and furthermore newly formed B cells in irradiated, reconstituted mice were not spatially related to the clonal progeny of CFU-s. Our present observations further define these pre-B cell populations and demonstrate by means of a monoclonal ant ibody that they may be distinguished from CFU-s from an early stage of embryonic life. These findings presage studies of factors that regulate lymphoid system development and raise interesting questions about initial events in the differentiation of this lineage. Among these are the following: (a) whether precommit ted cells arise at a very early age and have sufficient self-renewal and differentiation potential to obscure the subsequent contr ibution of less mature, uncommit ted stem cells, and (b) whether truly multipotential stem cells comprise a very small subpopulat ion of cells detected by the in vivo splenic focus (CFU-s) assay.