title: Generation of peripheral B cells occurs via two spatially and temporally distinct pathways.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Robert Coleman
authors.initials: RC
authors.lastname: Lindsley
authors.forename: Matthew
authors.initials: M
authors.lastname: Thomas
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Srivastava
authors.forename: David
authors.initials: D
authors.lastname: Allman
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D053264:B-Cell Activating Factor / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D001853:Bone Marrow / Q000276:immunology; D019013:CD40 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D015847:Interleukin-4 / Q000378:metabolism; D007700:Kinetics; D019041:L-Selectin / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D009154:Mutation / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011951:Receptors, Complement / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism; D013154:Spleen / Q000378:metabolism
chemical_list: D053264:B-Cell Activating Factor; D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D011951:Receptors, Complement; D017455:Receptors, IgE; C032402:complement 1q receptor; D019041:L-Selectin; D015847:Interleukin-4; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase