| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Ontario Cancer Institute and Department of Immunology, University of Toronto, Toronto, Ontario, Canada
The IL-7R and the pre-B cell receptor (pre-BCR) each provide critical signals during differentiation of B cell precursors. In this study we examine the interplay between signals dependent upon these receptors. We demonstrate that pre-BCR-deficient pro-B cells differ significantly from controls in their ability to use the IL-7R. We show that this difference, characterized by a failure to proliferate in response to IL-7, is narrowly restricted to IL-7 concentrations in the picogram per milliliter range and can be overcome with increasing amounts of IL-7. Restoration of Ig heavy chain to recombinase-activating gene-2-deficient pro-B cells leads to a restored response to picogram per milliliter levels of IL-7, providing strong evidence that modulation of the IL-7 dose-response threshold is dependent on pre-BCR. Culture of normal pro-B cells under low IL-7 conditions leads to selective outgrowth of cells expressing µ heavy chain, suggesting that modulation of IL-7 dose-response thresholds can allow for selective expansion of pre-BCR+ cells under conditions where IL-7 is limiting. We also provide evidence that expression of pre-BCR on pro-B cells limits the duration of IL-7 responsiveness by causing differentiation to an IL-7-unresponsive pre-B cell stage. Thus, the pre-BCR-dependent modulation of IL-7 responsiveness affects both the dose-response threshold and the duration of IL-7-induced clonal expansion. Our results suggest that positive selection of pre-BCR+ pro-B cells may be achieved through the fine tuning of IL-7 responses.
This article has been cited by other articles:
|
|
 |
|
  H. Brightbill and M. S. Schlissel The effects of c-Abl mutation on developing B cell differentiation and survival Int. Immunol., May 1, 2009; 21(5): 575 - 585. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Nakayama, M. Yamamoto, K. Hayashi, H. Satoh, K. Bundo, M. Kubo, R. Goitsuka, M. A. Farrar, and D. Kitamura BLNK suppresses pre-B-cell leukemogenesis through inhibition of JAK3 Blood, February 12, 2009; 113(7): 1483 - 1492. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. B. Guloglu, B. P. Smith, and C. A. J. Roman Multiple Levels of Selection Responsive to Immunoglobulin Light Chain and Heavy Chain Structures Impede the Development of D{micro}-Expressing B Cells J. Immunol., September 15, 2008; 181(6): 4098 - 4106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Anderson and R. Longnecker EBV LMP2A provides a surrogate pre-B cell receptor signal through constitutive activation of the ERK/MAPK pathway J. Gen. Virol., July 1, 2008; 89(7): 1563 - 1568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Wen, Y. Chen, L. Bai, G. Fu, J. Schuman, X. Dai, H. Zeng, C. Yang, R. P. Stephan, J. L. Cleveland, et al. Essential Role of Phospholipase C{gamma}2 in Early B-Cell Development and Myc-Mediated Lymphomagenesis Mol. Cell. Biol., December 15, 2006; 26(24): 9364 - 9376. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kawano, S. Yoshikawa, Y. Minegishi, and H. Karasuyama Pre-B Cell Receptor Assesses the Quality of IgH Chains and Tunes the Pre-B Cell Repertoire by Delivering Differential Signals J. Immunol., August 15, 2006; 177(4): 2242 - 2249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. B. Guloglu and C. A. J. Roman Precursor B Cell Receptor Signaling Activity Can Be Uncoupled from Surface Expression. J. Immunol., June 1, 2006; 176(11): 6862 - 6872. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. B. Guloglu, E. Bajor, B. P. Smith, and C. A. J. Roman The Unique Region of Surrogate Light Chain Component {lambda}5 Is a Heavy Chain-Specific Regulator of Precursor B Cell Receptor Signaling J. Immunol., July 1, 2005; 175(1): 358 - 366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Fuentes-Panana, G. Bannish, D. van der Voort, L. B. King, and J. G. Monroe Ig{alpha}/Ig{beta} Complexes Generate Signals for B Cell Development Independent of Selective Plasma Membrane Compartmentalization J. Immunol., February 1, 2005; 174(3): 1245 - 1252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Oliver, M. Wang, Y. Zhu, J. White, J. Kappler, and P. Marrack Loss of Bim Allows Precursor B Cell Survival But Not Precursor B Cell Differentiation in the Absence of Interleukin 7 J. Exp. Med., November 1, 2004; 200(9): 1179 - 1187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. E. Fleming, C. D. Milne, and C. J. Paige CD45-Deficient Mice Accumulate Pro-B Cells Both In Vivo and In Vitro J. Immunol., August 15, 2004; 173(4): 2542 - 2551. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. J. Vosshenrich, A. Cumano, W. Muller, J. P. Di Santo, and P. Vieira Pre-B cell receptor expression is necessary for thymic stromal lymphopoietin responsiveness in the bone marrow but not in the liver environment PNAS, July 27, 2004; 101(30): 11070 - 11075. [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]
|
|
|
|
|
|
T. Tretter, A. E. Ross, D. I. Dordai, and S. Desiderio Mimicry of Pre-B Cell Receptor Signaling by Activation of the Tyrosine Kinase Blk J. Exp. Med., December 15, 2003; 198(12): 1863 - 1873. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Otero and R. C. Rickert CD19 Function in Early and Late B Cell Development. II. CD19 Facilitates the Pro-B/Pre-B Transition J. Immunol., December 1, 2003; 171(11): 5921 - 5930. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Velazquez, A. M. Cheng, H. E. Fleming, C. Furlonger, S. Vesely, A. Bernstein, C. J. Paige, and T. Pawson Cytokine Signaling and Hematopoietic Homeostasis Are Disrupted in Lnk-deficient Mice J. Exp. Med., June 17, 2002; 195(12): 1599 - 1611. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Fry and C. L. Mackall Interleukin-7: from bench to clinic Blood, May 13, 2002; 99(11): 3892 - 3904. [Full Text] [PDF]
|
|
|
|
|
|
S. Middendorp, G. M. Dingjan, and R. W. Hendriks Impaired Precursor B Cell Differentiation in Bruton's Tyrosine Kinase-Deficient Mice J. Immunol., March 15, 2002; 168(6): 2695 - 2703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Bradl and H.-M. Jack Surrogate Light Chain-Mediated Interaction of a Soluble Pre-B Cell Receptor with Adherent Cell Lines J. Immunol., December 1, 2001; 167(11): 6403 - 6411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. H. Kline, T. A. Hayden, and P. Riegert The Initiation of B Cell Clonal Expansion Occurs Independently of Pre-B Cell Receptor Formation J. Immunol., November 1, 2001; 167(9): 5136 - 5142. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Lai and I. Goldschneider Cutting Edge: Identification of a Hybrid Cytokine Consisting of IL-7 and the {beta}-Chain of the Hepatocyte Growth Factor/Scatter Factor J. Immunol., October 1, 2001; 167(7): 3550 - 3554. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Stephan, E. Elgavish, H. Karasuyama, H. Kubagawa, and M. D. Cooper Analysis of VpreB Expression During B Lineage Differentiation in {lambda}5-Deficient Mice J. Immunol., October 1, 2001; 167(7): 3734 - 3739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Martinez-M., S. Minguet, P. Gonzalo, P. G. Soro, B. de Andres, A. Izcue, M. A. R. Marcos, and M.-L. Gaspar Long-lived polyclonal B-cell lines derived from midgestation mouse embryo lymphohematopoietic progenitors reconstitute adult immunodeficient mice Blood, September 15, 2001; 98(6): 1862 - 1871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Sandel, M. Gendelman, G. Kelsoe, and J. G. Monroe Definition of a Novel Cellular Constituent of the Bone Marrow That Regulates the Response of Immature B Cells to B Cell Antigen Receptor Engagement J. Immunol., May 15, 2001; 166(10): 5935 - 5944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Mojica, S. S. Perry, A. E. Searles, K. S. J. Elenitoba-Johnson, L. J. Pierce, A. Wiesmann, W. B. Slayton, and G. J. Spangrude Phenotypic Distinction and Functional Characterization of Pro-B Cells in Adult Mouse Bone Marrow J. Immunol., March 1, 2001; 166(5): 3042 - 3051. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Yun, M. D. Tallquist, A. Aicher, K. L. Rafferty, A. J. Marshall, J. J. Moon, M. K. Ewings, M. Mohaupt, S. W. Herring, and E. A. Clark Osteoprotegerin, a Crucial Regulator of Bone Metabolism, Also Regulates B Cell Development and Function J. Immunol., February 1, 2001; 166(3): 1482 - 1491. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Okada, T. Yoshida, Z. Hong, G. Ishii, M. Hatano, M. Kuro-o, Y. Nabeshima, Y.-i. Nabeshima, and T. Tokuhisa Impairment of B lymphopoiesis in precocious aging (klotho) mice Int. Immunol., June 1, 2000; 12(6): 861 - 871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Kato, T. Miyazaki, T. Nakamura, and A. Kudo Inducible differentiation and apoptosis of the pre-B cell receptor-positive pre-B cell line Int. Immunol., March 1, 2000; 12(3): 325 - 334. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Wei, R. Zeff, and I. Goldschneider Murine Pro-B Cells Require IL-7 and Its Receptor Complex to Up-Regulate IL-7R{alpha}, Terminal Deoxynucleotidyltransferase, and c{micro} Expression J. Immunol., February 15, 2000; 164(4): 1961 - 1970. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Carsetti The Development of B Cells in the Bone Marrow Is Controlled by the Balance Between Cell-autonomous Mechanisms and Signals from the Microenvironment J. Exp. Med., January 3, 2000; 191(1): 5 - 8. [Full Text] [PDF]
|
|
|
|
|
|
Y. Yamashita, K. Oritani, E. K. Miyoshi, R. Wall, M. Bernfield, and P. W. Kincade Syndecan-4 Is Expressed by B Lineage Lymphocytes and Can Transmit a Signal for Formation of Dendritic Processes J. Immunol., May 15, 1999; 162(10): 5940 - 5948. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hess, A. Werner, T. Wirth, F. Melchers, H.-M. Jack, and T. H. Winkler Induction of pre-B cell proliferation after de novo synthesis of the pre-B cell receptor PNAS, February 13, 2001; 98(4): 1745 - 1750. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
