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 Blood, 15 March 2007, Vol. 109, No. 6, pp. 2521-2528.
Prepublished online as a Blood First Edition Paper on November 14, 2006; DOI 10.1182/blood-2006-04-018085.

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IMMUNOBIOLOGY

Generation of peripheral B cells occurs via two spatially and temporally distinct pathways

Robert Coleman Lindsley1, Matthew Thomas1, Bhaskar Srivastava1, and David Allman1

1 Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA

We have identified a population of newly formed bone marrow (BM) B cells that shares multiple characteristics with late transitional B cells in the spleen. Both late splenic transitional B cells and cells within this uncharacterized BM population expressed the cell-surface phenotype AA4+ CD23+, yet the developmental kinetics and the renewal rate of AA4+ CD23+ BM B cells mirrored recently formed BM B cells. Further, unlike the least mature B cells in the BM and spleen, AA4+ CD23+ BM B cells expressed the homing receptor CD62L, were dependent on the antiapoptotic cytokine receptor BR3 and the tec family kinase Btk, and proliferated in response to IL-4 plus CD40 stimulation. Finally, frequencies of {lambda} light chain-positive B cells declined among AA4+ CD23+ B cells in both the BM and spleen, suggesting that V-gene selection events correlate with CD23 expression in both compartments. These observations indicate that the first step in B-cell maturation occurs in both the BM and the periphery and suggest that recently formed B cells exit the BM as a heterogeneous pool of immature and semimature B cells.


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