| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
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.
This article has been cited by other articles:
|
|
 |
|
  M. M. Tomayko, S. M. Anderson, C. E. Brayton, S. Sadanand, N. C. Steinel, T. W. Behrens, and M. J. Shlomchik Systematic Comparison of Gene Expression between Murine Memory and Naive B Cells Demonstrates That Memory B Cells Have Unique Signaling Capabilities J. Immunol., July 1, 2008; 181(1): 27 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Shimomura, A. Ogawa, M. Kawada, K. Sugimoto, E. Mizoguchi, H.-N. Shi, S. Pillai, A. K. Bhan, and A. Mizoguchi A unique B2 B cell subset in the intestine J. Exp. Med., June 9, 2008; 205(6): 1343 - 1355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Tarlinton Sheepish B cells: evidence for antigen-independent antibody diversification in humans and mice J. Exp. Med., June 9, 2008; 205(6): 1251 - 1254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kiefer, P. B. Nakajima, J. Oshinsky, S. H. Seeholzer, M. Radic, G. C. Bosma, and M. J. Bosma Antigen Receptor Editing in Anti-DNA Transitional B Cells Deficient for Surface IgM J. Immunol., May 1, 2008; 180(9): 6094 - 6106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Pathak, S. Ma, L. Trinh, and R. Lu A Role for Interferon Regulatory Factor 4 in Receptor Editing Mol. Cell. Biol., April 15, 2008; 28(8): 2815 - 2824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Meyer-Bahlburg, S. F. Andrews, K. O.A. Yu, S. A. Porcelli, and D. J. Rawlings Characterization of a late transitional B cell population highly sensitive to BAFF-mediated homeostatic proliferation J. Exp. Med., January 21, 2008; 205(1): 155 - 168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Chen, B. L. Esplin, K. P. Garrett, R. S. Welner, C. F. Webb, and P. W. Kincade Retinoids Accelerate B Lineage Lymphoid Differentiation J. Immunol., January 1, 2008; 180(1): 138 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wang, J. Feng, C.-F. Qi, Z. Li, H. C. Morse III, and S. H. Clarke Transitional B Cells Lose Their Ability to Receptor Edit but Retain Their Potential for Positive and Negative Selection J. Immunol., December 1, 2007; 179(11): 7544 - 7552. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Choudhury, P. L. Cohen, and R. A. Eisenberg Mature B Cells Preferentially Lose Tolerance in the Chronic Graft-versus-Host Disease Model of Systemic Lupus Erythematosus J. Immunol., October 15, 2007; 179(8): 5564 - 5570. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Cariappa, C. Boboila, S. T. Moran, H. Liu, H. N. Shi, and S. Pillai The Recirculating B Cell Pool Contains Two Functionally Distinct, Long-Lived, Posttransitional, Follicular B Cell Populations J. Immunol., August 15, 2007; 179(4): 2270 - 2281. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. N. Teague, Y. Pan, P. A. Mudd, B. Nakken, Q. Zhang, P. Szodoray, X. Kim-Howard, P. C. Wilson, and A. D. Farris Cutting Edge: Transitional T3 B Cells Do Not Give Rise to Mature B Cells, Have Undergone Selection, and Are Reduced in Murine Lupus J. Immunol., June 15, 2007; 178(12): 7511 - 7515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Evans, K. A. Chavez-Rueda, A. Eddaoudi, A. Meyer-Bahlburg, D. J. Rawlings, M. R. Ehrenstein, and C. Mauri Novel Suppressive Function of Transitional 2 B Cells in Experimental Arthritis J. Immunol., June 15, 2007; 178(12): 7868 - 7878. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Debnath, K. M. Roundy, J. J. Weis, and J. H. Weis Defining In Vivo Transcription Factor Complexes of the Murine CD21 and CD23 Genes J. Immunol., June 1, 2007; 178(11): 7139 - 7150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. D. Hondowicz, S. T. Alexander, W. J. Quinn III, A. J. Pagan, M. H. Metzgar, M. P. Cancro, and J. Erikson The role of BLyS/BLyS receptors in anti-chromatin B cell regulation Int. Immunol., April 1, 2007; 19(4): 465 - 475. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. van Zelm, T. Szczepanski, M. van der Burg, and J. J.M. van Dongen Replication history of B lymphocytes reveals homeostatic proliferation and extensive antigen-induced B cell expansion J. Exp. Med., March 19, 2007; 204(3): 645 - 655. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ueda, D. Liao, K. Yang, A. Patel, and G. Kelsoe T-Independent Activation-Induced Cytidine Deaminase Expression, Class-Switch Recombination, and Antibody Production by Immature/Transitional 1 B Cells J. Immunol., March 15, 2007; 178(6): 3593 - 3601. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C. Lindsley, M. Thomas, B. Srivastava, and D. Allman Generation of peripheral B cells occurs via two spatially and temporally distinct pathways Blood, March 15, 2007; 109(6): 2521 - 2528. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Cariappa, C. Chase, H. Liu, P. Russell, and S. Pillai Naive recirculating B cells mature simultaneously in the spleen and bone marrow Blood, March 15, 2007; 109(6): 2339 - 2345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Shankar, J. C. Nixon, S. Maier, J. Workman, A. D. Farris, and C. F. Webb Anti-Nuclear Antibody Production and Autoimmunity in Transgenic Mice That Overexpress the Transcription Factor Bright J. Immunol., March 1, 2007; 178(5): 2996 - 3006. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Llorian, Z. Stamataki, S. Hill, M. Turner, and I.-L. Martensson Cutting Edge: The PI3K p110{delta} Is Required for Down-Regulation of RAG Expression in Immature B Cells J. Immunol., February 15, 2007; 178(4): 1981 - 1985. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Stephenson, A. V. Miletic, T. Kloeppel, S. Kusin, and W. Swat Vav Proteins Regulate the Plasma Cell Program and Secretory Ig Production J. Immunol., December 15, 2006; 177(12): 8620 - 8625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-J. Won, J. B. Foote, M. R. Odom, J. Pan, J. F. Kearney, and R. S. Davis Fc Receptor Homolog 3 Is a Novel Immunoregulatory Marker of Marginal Zone and B1 B Cells J. Immunol., November 15, 2006; 177(10): 6815 - 6823. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Silveira, H. D. Chapman, J. Stolp, E. Johnson, S. L. Cox, K. Hunter, L. S. Wicker, and D. V. Serreze Genes within the Idd5 and Idd9/11 Diabetes Susceptibility Loci Affect the Pathogenic Activity of B Cells in Nonobese Diabetic Mice J. Immunol., November 15, 2006; 177(10): 7033 - 7041. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M P Cancro The BLyS/BAFF family of ligands and receptors: key targets in the therapy and understanding of autoimmunity Ann Rheum Dis, November 1, 2006; 65(suppl_3): iii34 - iii36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Hoek, P. Antony, J. Lowe, N. Shinners, B. Sarmah, S. R. Wente, D. Wang, R. M. Gerstein, and W. N. Khan Transitional B Cell Fate Is Associated with Developmental Stage-Specific Regulation of Diacylglycerol and Calcium Signaling upon B Cell Receptor Engagement J. Immunol., October 15, 2006; 177(8): 5405 - 5413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Vinay, J. D. Kim, and B. S. Kwon Amelioration of Mercury-Induced Autoimmunity by 4-1BB J. Immunol., October 15, 2006; 177(8): 5708 - 5717. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Tian, M. Beardall, Y. Xu, J. Li, D. C. Parker, N. Casanova, A. C. Bakke, and C. Chen B Cells Expressing a Natural Polyreactive Autoantibody Have a Distinct Phenotype and Are Overrepresented in Immunoglobulin Heavy Chain Transgenic Mice J. Immunol., August 15, 2006; 177(4): 2412 - 2422. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. C. Harman, J. P. Miller, N. Nikbakht, R. Gerstein, and D. Allman Mouse plasmacytoid dendritic cells derive exclusively from estrogen-resistant myeloid progenitors Blood, August 1, 2006; 108(3): 878 - 885. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Lesley, L. M. Kelly, Y. Xu, and J. G. Cyster Naive CD4 T cells constitutively express CD40L and augment autoreactive B cell survival PNAS, July 11, 2006; 103(28): 10717 - 10722. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. C. Ippolito, R. L. Schelonka, M. Zemlin, I. I. Ivanov, R. Kobayashi, C. Zemlin, G. L. Gartland, L. Nitschke, J. Pelkonen, K. Fujihashi, et al. Forced usage of positively charged amino acids in immunoglobulin CDR-H3 impairs B cell development and antibody production J. Exp. Med., June 12, 2006; 203(6): 1567 - 1578. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Miller, J. E. Stadanlick, and M. P. Cancro Space, Selection, and Surveillance: Setting Boundaries with BLyS. J. Immunol., June 1, 2006; 176(11): 6405 - 6410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Sekiguchi, L. Yunk, D. Gary, D. Charan, B. Srivastava, D. Allman, M. G. Weigert, and E. T. L. Prak Development and Selection of Edited B Cells in B6.56R Mice. J. Immunol., June 1, 2006; 176(11): 6879 - 6887. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Oliver, T. Vass, J. Kappler, and P. Marrack Loss of the proapoptotic protein, Bim, breaks B cell anergy J. Exp. Med., March 20, 2006; 203(3): 731 - 741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Huang, J. F. Kearney, M. J. Grusby, C. Benoist, and D. Mathis Induction of tolerance in arthritogenic B cells with receptors of differing affinity for self-antigen PNAS, March 7, 2006; 103(10): 3734 - 3739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Grimaldi, V. Jeganathan, and B. Diamond Hormonal Regulation of B Cell Development: 17beta-Estradiol Impairs Negative Selection of High-Affinity DNA-Reactive B Cells at More Than One Developmental Checkpoint. J. Immunol., March 1, 2006; 176(5): 2703 - 2710. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Malaspina, S. Moir, J. Ho, W. Wang, M. L. Howell, M. A. O'Shea, G. A. Roby, C. A. Rehm, J. M. Mican, T.-W. Chun, et al. Appearance of immature/transitional B cells in HIV-infected individuals with advanced disease: Correlation with increased IL-7 PNAS, February 14, 2006; 103(7): 2262 - 2267. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K. Cuss, D. T. Avery, J. L. Cannons, L. J. Yu, K. E. Nichols, P. J. Shaw, and S. G. Tangye Expansion of Functionally Immature Transitional B Cells Is Associated with Human-Immunodeficient States Characterized by Impaired Humoral Immunity J. Immunol., February 1, 2006; 176(3): 1506 - 1516. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H. Skalet, J. A. Isler, L. B. King, H. P. Harding, D. Ron, and J. G. Monroe Rapid B Cell Receptor-induced Unfolded Protein Response in Nonsecretory B Cells Correlates with Pro- Versus Antiapoptotic Cell Fate J. Biol. Chem., December 2, 2005; 280(48): 39762 - 39771. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Srivastava, W. J. Quinn III, K. Hazard, J. Erikson, and D. Allman Characterization of marginal zone B cell precursors J. Exp. Med., November 7, 2005; 202(9): 1225 - 1234. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zheng, S. Gallucci, J. P. Gaughan, J. A. Gross, and M. Monestier A Role for B Cell-Activating Factor of the TNF Family in Chemically Induced Autoimmunity J. Immunol., November 1, 2005; 175(9): 6163 - 6168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Wither, C. Loh, G. Lajoie, S. Heinrichs, Y.-C. Cai, G. Bonventi, and R. MacLeod Colocalization of Expansion of the Splenic Marginal Zone Population with Abnormal B Cell Activation and Autoantibody Production in B6 Mice with an Introgressed New Zealand Black Chromosome 13 Interval J. Immunol., October 1, 2005; 175(7): 4309 - 4319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Vigorito, L. Gambardella, F. Colucci, S. McAdam, and M. Turner Vav proteins regulate peripheral B-cell survival Blood, October 1, 2005; 106(7): 2391 - 2398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Takeuchi, J. Fisher, H. Suh, H. Harada, B. A. Malynn, and S. J. Korsmeyer Essential role of BAX,BAK in B cell homeostasis and prevention of autoimmune disease PNAS, August 9, 2005; 102(32): 11272 - 11277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. YOUINOU, C. JAMIN, J.-O. PERS, C. BERTHOU, A. SARAUX, and Y. RENAUDINEAU B Lymphocytes Are Required for Development and Treatment of Autoimmune Diseases Ann. N.Y. Acad. Sci., June 1, 2005; 1050(1): 19 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Hayashi, S. Akira, and A. Nobrega Role of TLR in B Cell Development: Signaling through TLR4 Promotes B Cell Maturation and Is Inhibited by TLR2 J. Immunol., June 1, 2005; 174(11): 6639 - 6647. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. P. Sims, R. Ettinger, Y. Shirota, C. H. Yarboro, G. G. Illei, and P. E. Lipsky Identification and characterization of circulating human transitional B cells Blood, June 1, 2005; 105(11): 4390 - 4398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. G. Phan, S. Gardam, A. Basten, and R. Brink Altered Migration, Recruitment, and Somatic Hypermutation in the Early Response of Marginal Zone B Cells to T Cell-Dependent Antigen J. Immunol., April 15, 2005; 174(8): 4567 - 4578. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Grimaldi, R. Hicks, and B. Diamond B Cell Selection and Susceptibility to Autoimmunity J. Immunol., February 15, 2005; 174(4): 1775 - 1781. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Donahue, K. L. Hess, K. L. Ng, and D. A. Fruman Altered splenic B cell subset development in mice lacking phosphoinositide 3-kinase p85{alpha} Int. Immunol., December 1, 2004; 16(12): 1789 - 1798. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. S. M. Rahman and T. Manser B Cells Expressing Bcl-2 and a Signaling-Impaired BAFF-Specific Receptor Fail to Mature and Are Deficient in the Formation of Lymphoid Follicles and Germinal Centers J. Immunol., November 15, 2004; 173(10): 6179 - 6188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ozaki, R. Spolski, R. Ettinger, H.-P. Kim, G. Wang, C.-F. Qi, P. Hwu, D. J. Shaffer, S. Akilesh, D. C. Roopenian, et al. Regulation of B Cell Differentiation and Plasma Cell Generation by IL-21, a Novel Inducer of Blimp-1 and Bcl-6 J. Immunol., November 1, 2004; 173(9): 5361 - 5371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Maillard, A. P. Weng, A. C. Carpenter, C. G. Rodriguez, H. Sai, L. Xu, D. Allman, J. C. Aster, and W. S. Pear Mastermind critically regulates Notch-mediated lymphoid cell fate decisions Blood, September 15, 2004; 104(6): 1696 - 1702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
