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*
Department of Pathology and Laboratory Medicine and Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104; and
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111
Although immature/transitional peripheral B cells may remain susceptible to selection pressures before full maturation, the nature and timing of these selection events remain unclear. We show that correlated expression of surface (s) IgM (sIgM), CD23, and AA4 defines three nonproliferative subpopulations of immature/transitional peripheral B cells. We designate these populations transitional (T) 1 (AA4+CD23-sIgMhigh), T2 (AA4+CD23+sIgMhigh), and T3 (AA4+CD23+sIgMlow). Cells within all three subsets are functionally immature as judged by their failure to proliferate following sIgM cross-linking in vitro, and their rapid rate of turnover in vivo as assessed by 5-bromo-2'-deoxyuridine labeling. These labeling studies also reveal measurable cell loss at both the T1-T2 and T2-T3 transitions, suggesting the existence of multiple selection points within the peripheral immature B cell pool. Furthermore, we find that Btk-deficient (xid) mice exhibit an incomplete developmental block at the T2-T3 transition within the immature B cell pool. This contrasts markedly with lyn-/- mice, which exhibit depressed numbers but normal ratios of each immature peripheral B cell subset and severely reduced numbers of mature B cells. Together, these data provide evidence for multiple selection points among immature peripheral B cells, suggesting that the B cell repertoire is shaped by multiple unique selection events that occur within the immature/transitional peripheral B cell pool.
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T. C. Chiles Regulation and Function of Cyclin D2 in B Lymphocyte Subsets J. Immunol., September 1, 2004; 173(5): 2901 - 2907. [Abstract] [Full Text] [PDF]
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Y. Sasaki, S. Casola, J. L. Kutok, K. Rajewsky, and M. Schmidt-Supprian TNF Family Member B Cell-Activating Factor (BAFF) Receptor-Dependent and -Independent Roles for BAFF in B Cell Physiology J. Immunol., August 15, 2004; 173(4): 2245 - 2252. [Abstract] [Full Text] [PDF]
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G. Shahaf, D. Allman, M. P. Cancro, and R. Mehr Screening of alternative models for transitional B cell maturation Int. Immunol., August 1, 2004; 16(8): 1081 - 1090. [Abstract] [Full Text] [PDF]
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E. M. Fuentes-Panana, G. Bannish, N. Shah, and J. G. Monroe Basal Ig{alpha}/Ig{beta} Signals Trigger the Coordinated Initiation of Pre-B Cell Antigen Receptor-Dependent Processes J. Immunol., July 15, 2004; 173(2): 1000 - 1011. [Abstract] [Full Text] [PDF]
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M. P. Cancro and J. F. Kearney B Cell Positive Selection: Road Map to the Primary Repertoire? J. Immunol., July 1, 2004; 173(1): 15 - 19. [Abstract] [Full Text] [PDF]
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S. O'Connor, S. D. Shumway, I. J. Amanna, C. E. Hayes, and S. Miyamoto Regulation of Constitutive p50/c-Rel Activity via Proteasome Inhibitor-Resistant I{kappa}B{alpha} Degradation in B Cells Mol. Cell. Biol., June 1, 2004; 24(11): 4895 - 4908. [Abstract] [Full Text] [PDF]
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C. E. Blanco-Betancourt, A. Moncla, M. Milili, Y. L. Jiang, E. M. Viegas-Pequignot, B. Roquelaure, I. Thuret, and C. Schiff Defective B-cell-negative selection and terminal differentiation in the ICF syndrome Blood, April 1, 2004; 103(7): 2683 - 2690. [Abstract] [Full Text] [PDF]
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S. Middendorp and R. W. Hendriks Cellular Maturation Defects in Bruton's Tyrosine Kinase-Deficient Immature B Cells Are Amplified by Premature B Cell Receptor Expression and Reduced by Receptor Editing J. Immunol., February 1, 2004; 172(3): 1371 - 1379. [Abstract] [Full Text] [PDF]
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L. Heltemes-Harris, X. Liu, and T. Manser Progressive Surface B Cell Antigen Receptor Down-Regulation Accompanies Efficient Development of Antinuclear Antigen B Cells to Mature, Follicular Phenotype J. Immunol., January 15, 2004; 172(2): 823 - 833. [Abstract] [Full Text] [PDF]
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H. Wang and S. H. Clarke Evidence for a Ligand-Mediated Positive Selection Signal in Differentiation to a Mature B Cell J. Immunol., December 15, 2003; 171(12): 6381 - 6388. [Abstract] [Full Text] [PDF]
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S. Middendorp, G. M. Dingjan, A. Maas, K. Dahlenborg, and R. W. Hendriks Function of Bruton's Tyrosine Kinase during B Cell Development Is Partially Independent of Its Catalytic Activity J. Immunol., December 1, 2003; 171(11): 5988 - 5996. [Abstract] [Full Text] [PDF]
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Z. SM. Rahman, S. P. Rao, S. L. Kalled, and T. Manser Normal Induction but Attenuated Progression of Germinal Center Responses in BAFF and BAFF-R Signaling-Deficient Mice J. Exp. Med., October 20, 2003; 198(8): 1157 - 1169. [Abstract] [Full Text] [PDF]
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N. Zhang, J. Guo, and Y.-W. He Lymphocyte Accumulation in the Spleen of Retinoic Acid Receptor-Related Orphan Receptor {gamma}-Deficient Mice J. Immunol., August 15, 2003; 171(4): 1667 - 1675. [Abstract] [Full Text] [PDF]
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S. H. Smith and M. P. Cancro Cutting Edge: B Cell Receptor Signals Regulate BLyS Receptor Levels in Mature B Cells and Their Immediate Progenitors J. Immunol., June 15, 2003; 170(12): 5820 - 5823. [Abstract] [Full Text] [PDF]
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I. J. Amanna, J. P. Dingwall, and C. E. Hayes Enforced bcl-xL Gene Expression Restored Splenic B Lymphocyte Development in BAFF-R Mutant Mice J. Immunol., May 1, 2003; 170(9): 4593 - 4600. [Abstract] [Full Text] [PDF]
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D. Tarlinton, A. Light, D. Metcalf, R. P. Harvey, and L. Robb Architectural Defects in the Spleens of Nkx2-3-Deficient Mice Are Intrinsic and Associated with Defects in Both B Cell Maturation and T Cell-Dependent Immune Responses J. Immunol., April 15, 2003; 170(8): 4002 - 4010. [Abstract] [Full Text] [PDF]
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R. Mehr, G. Shahaf, A. Sah, and M. Cancro Asynchronous differentiation models explain bone marrow labeling kinetics and predict reflux between the pre- and immature B cell pools Int. Immunol., March 1, 2003; 15(3): 301 - 312. [Abstract] [Full Text] [PDF]
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H. Dalwadi, B. Wei, M. Schrage, T. T. Su, D. J. Rawlings, and J. Braun B Cell Developmental Requirement for the G{alpha}i2 Gene J. Immunol., February 15, 2003; 170(4): 1707 - 1715. [Abstract] [Full Text] [PDF]
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