Submitted April 19, 2006
Accepted October 23, 2006
Generation of peripheral B cells occurs via two spatially and temporally distinct pathways
Robert Coleman Lindsley, Matthew Thomas, Bhaskar Srivastava, and David Allman*
Dept of Pathology & Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA
* Corresponding author; email: dallman{at}mail.med.upenn.edu.
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 anti-apoptotic cytokine receptor BR3 and the tec family kinase Btk, and proliferated in response to IL-4 plus CD40 stimulation. Finally, frequencies of 
light chain+ 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 semi-mature B cells.
