B-cell differentiation and maturation in the bone marrow : heterogeneity of B-cell precursors assessed by the appearance of age-related markers in functionally defined populations

We have used a functional in vitro assay to define several populations of B-cell and B-cell precursors normally present in the murine bone marrow. A multi-parameter analysis of cells (including size, polyclonal activation requirements and kinetics of recruitment to IgM secretion, membrane IgM expression, nylon-wool adherence properties and proliferative status) has permitted the resolution of up to 10 populations. Cells showing a delayed kinetics of development to plasma cells as compared to small B-lymphocytes were also found immature with respect to age-related markers. The appearance of characteristic markers (nylon wood adherence, membrane IgM) and functional properties (LPS-responsiveness) was traced within distinguishable populations of cells. On the basis of functional properties (AE-dependence, LPS-responsiveness and time of peak response) these 10 populations were grouped into 3 distinct subsets. From the major discontinuities in the kinetics of individual parameters and from changes in the quantitative expression of age-related markers, these subsets were sequentially related into the following scheme:pre-B cells (--->) early B cells (--->) B-lymphocytesFinally, a proliferative pathway was found within the early B cell compartment which parallels the post-mitotic maturation of the pre-B cell progeny