This analysis of B cell development as a function of age reveals a relatively widespread distribution of progenitor B (pro-B), pre-B, and B cells in fetal tissues, and thus supports the idea of a multifocal origin of B lineage cells during embryonic development. From mid-gestation onward, the bone marrow is the major site of B cell generation in humans. A relatively constant ratio of bone marrow precursors to B cells of immature phenotype (CD24highCD10+CD20lowIgD-) is maintained from mid-gestation through the eighth decade of life. The persistence of recombinase gene activity in pro-B cells further attests the sustained production of B cells in bone marrow. Interestingly, a subpopulation of B cells with mature phenotype (CD24lowCD10-CD20highIgD+) accumulates in the bone marrow during childhood, and this becomes the predominant B cell subpopulation in adult bone marrow. This mature population of bone marrow B cells may represent a subpopulation of recirculating B cells that have undergone selection in the periphery.

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