| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases and
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892
IL-21 is a type I cytokine that influences the function of T cells, NK cells, and B cells. In this study, we report that IL-21 plays a major role in stimulating the differentiation of human B cells. When human B cells were stimulated through the BCR, IL-21 induced minimal proliferation, IgD down-modulation, and small numbers of plasma cells. In contrast, after CD40 engagement, IL-21 induced extensive proliferation, class switch recombination (CSR), and plasma cell differentiation. Upon cross-linking both BCR and CD40, IL-21 induced the largest numbers of plasma cells. IL-21 drove both postswitch memory cells as well as poorly responsive naive cord blood B cells to differentiate into plasma cells. The effect of IL-21 was more potent than the combination of IL-2 and IL-10, especially when responsiveness of cord blood B cells was examined. IL-21 costimulation potently induced the expression of both B lymphocyte-induced maturation protein-1 (BLIMP-1) and activation-induced cytidine deaminase as well as the production of large amounts of IgG from B cells. Despite the induction of activation-induced cytidine deaminase and CSR, IL-21 did not induce somatic hypermutation. Finally, IL-2 enhanced the effects of IL-21, whereas IL-4 inhibited IL-21-induced plasma cell differentiation. Taken together, our data show that IL-21 plays a central role in CSR and plasma cell differentiation during T cell-dependent B cell responses.
This article has been cited by other articles:
|
|
 |
|
  H. Wu, E. Center, G. Tsokos, and H. Weiner Suppression of murine SLE by oral anti-CD3: inducible CD4+CD25-LAP+ regulatory T cells control the expansion of IL-17+ follicular helper T cells Lupus, June 1, 2009; 18(7): 586 - 596. [Abstract] [PDF]
|
|
|
|
 |
|
 V. Pistoia and C. Cocco IL-21: a new player in the control of isotype switch in Peyer's patches J. Leukoc. Biol., May 1, 2009; 85(5): 739 - 743. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-Y. Seo, J. Youn, and P.-H. Kim IL-21 ensures TGF-{beta}1-induced IgA isotype expression in mouse Peyer's patches J. Leukoc. Biol., May 1, 2009; 85(5): 744 - 750. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. S. Longo, P. L. Lugar, S. Yavuz, W. Zhang, P. H. L. Krijger, D. E. Russ, D. D. Jima, S. S. Dave, A. C. Grammer, and P. E. Lipsky Analysis of somatic hypermutation in X-linked hyper-IgM syndrome shows specific deficiencies in mutational targeting Blood, April 16, 2009; 113(16): 3706 - 3715. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Lee, S. Kuchen, R. Fischer, S. Chang, and P. E. Lipsky Identification and Characterization of a Human CD5+ Pre-Naive B Cell Population J. Immunol., April 1, 2009; 182(7): 4116 - 4126. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-T. Su, H.-Y. Ying, Y.-K. Chiu, F.-R. Lin, M.-Y. Chen, and K.-I Lin Involvement of Histone Demethylase LSD1 in Blimp-1-Mediated Gene Repression during Plasma Cell Differentiation Mol. Cell. Biol., March 15, 2009; 29(6): 1421 - 1431. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Spolski, H.-P. Kim, W. Zhu, D. E. Levy, and W. J. Leonard IL-21 Mediates Suppressive Effects via Its Induction of IL-10 J. Immunol., March 1, 2009; 182(5): 2859 - 2867. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Konforte, N. Simard, and C. J. Paige IL-21: An Executor of B Cell Fate J. Immunol., February 15, 2009; 182(4): 1781 - 1787. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Bubier, T. J. Sproule, O. Foreman, R. Spolski, D. J. Shaffer, H. C. Morse III, W. J. Leonard, and D. C. Roopenian A critical role for IL-21 receptor signaling in the pathogenesis of systemic lupus erythematosus in BXSB-Yaa mice PNAS, February 3, 2009; 106(5): 1518 - 1523. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Dienz, S. M. Eaton, J. P. Bond, W. Neveu, D. Moquin, R. Noubade, E. M. Briso, C. Charland, W. J. Leonard, G. Ciliberto, et al. The induction of antibody production by IL-6 is indirectly mediated by IL-21 produced by CD4+ T cells J. Exp. Med., January 16, 2009; 206(1): 69 - 78. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R Ettinger, S Kuchen, and P E Lipsky Interleukin 21 as a target of intervention in autoimmune disease Ann Rheum Dis, December 1, 2008; 67(Suppl_3): iii83 - iii86. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Kinter, E. J. Godbout, J. P. McNally, I. Sereti, G. A. Roby, M. A. O'Shea, and A. S. Fauci The Common {gamma}-Chain Cytokines IL-2, IL-7, IL-15, and IL-21 Induce the Expression of Programmed Death-1 and Its Ligands J. Immunol., November 15, 2008; 181(10): 6738 - 6746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Y. Wu, F. J. Quintana, and H. L. Weiner Nasal Anti-CD3 Antibody Ameliorates Lupus by Inducing an IL-10-Secreting CD4+CD25-LAP+ Regulatory T Cell and Is Associated with Down-Regulation of IL-17+CD4+ICOS+CXCR5+ Follicular Helper T Cells J. Immunol., November 1, 2008; 181(9): 6038 - 6050. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-M. Tsai, Y.-K. Chiu, T.-L. Hsu, I-Y. Lin, S.-L. Hsieh, and K.-I Lin Galectin-1 Promotes Immunoglobulin Production during Plasma Cell Differentiation J. Immunol., October 1, 2008; 181(7): 4570 - 4579. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Schmidlin, S. A. Diehl, M. Nagasawa, F. A. Scheeren, R. Schotte, C. H. Uittenbogaart, H. Spits, and B. Blom Spi-B inhibits human plasma cell differentiation by repressing BLIMP1 and XBP-1 expression Blood, September 1, 2008; 112(5): 1804 - 1812. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. T. Avery, C. S. Ma, V. L. Bryant, B. Santner-Nanan, R. Nanan, M. Wong, D. A. Fulcher, M. C. Cook, and S. G. Tangye STAT3 is required for IL-21-induced secretion of IgE from human naive B cells Blood, September 1, 2008; 112(5): 1784 - 1793. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. J. Leonard, R. Zeng, and R. Spolski Interleukin 21: a cytokine/cytokine receptor system that has come of age J. Leukoc. Biol., August 1, 2008; 84(2): 348 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. T. Avery, V. L. Bryant, C. S. Ma, R. de Waal Malefyt, and S. G. Tangye IL-21-Induced Isotype Switching to IgG and IgA by Human Naive B Cells Is Differentially Regulated by IL-4 J. Immunol., August 1, 2008; 181(3): 1767 - 1779. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Nie, M. Gomez, P. Landgraf, J.-F. Garcia, Y. Liu, L. H.C. Tan, A. Chadburn, T. Tuschl, D. M. Knowles, and W. Tam MicroRNA-Mediated Down-Regulation of PRDM1/Blimp-1 in Hodgkin/Reed-Sternberg Cells: A Potential Pathogenetic Lesion in Hodgkin Lymphomas Am. J. Pathol., July 1, 2008; 173(1): 242 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Hinrichs, R. Spolski, C. M. Paulos, L. Gattinoni, K. W. Kerstann, D. C. Palmer, C. A. Klebanoff, S. A. Rosenberg, W. J. Leonard, and N. P. Restifo IL-2 and IL-21 confer opposing differentiation programs to CD8+ T cells for adoptive immunotherapy Blood, June 1, 2008; 111(11): 5326 - 5333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Diehl, H. Schmidlin, M. Nagasawa, S. D. van Haren, M. J. Kwakkenbos, E. Yasuda, T. Beaumont, F. A. Scheeren, and H. Spits STAT3-Mediated Up-Regulation of BLIMP1 Is Coordinated with BCL6 Down-Regulation to Control Human Plasma Cell Differentiation J. Immunol., April 1, 2008; 180(7): 4805 - 4815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A H Sawalha, K M Kaufman, J A Kelly, A J Adler, T Aberle, J Kilpatrick, E K Wakeland, Q-Z Li, A E Wandstrat, D R Karp, et al. Genetic association of interleukin-21 polymorphisms with systemic lupus erythematosus Ann Rheum Dis, April 1, 2008; 67(4): 458 - 461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.-K. Shirakawa, D. Nagakubo, K. Hieshima, T. Nakayama, Z. Jin, and O. Yoshie 1,25-Dihydroxyvitamin D3 Induces CCR10 Expression in Terminally Differentiating Human B Cells J. Immunol., March 1, 2008; 180(5): 2786 - 2795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. L. Bryant, C. S. Ma, D. T. Avery, Y. Li, K. L. Good, L. M. Corcoran, R. de Waal Malefyt, and S. G. Tangye Cytokine-Mediated Regulation of Human B Cell Differentiation into Ig-Secreting Cells: Predominant Role of IL-21 Produced by CXCR5+ T Follicular Helper Cells J. Immunol., December 15, 2007; 179(12): 8180 - 8190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kishida, Y. Hiromura, M. Shin-Ya, H. Asada, H. Kuriyama, M. Sugai, A. Shimizu, Y. Yokota, T. Hama, J. Imanishi, et al. IL-21 Induces Inhibitor of Differentiation 2 and Leads to Complete Abrogation of Anaphylaxis in Mice J. Immunol., December 15, 2007; 179(12): 8554 - 8561. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. D. Davis, K. Skak, M. J. Smyth, P. E.G. Kristjansen, D. M. Miller, and P. V. Sivakumar Interleukin-21 Signaling: Functions in Cancer and Autoimmunity Clin. Cancer Res., December 1, 2007; 13(23): 6926 - 6932. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Wei, A. Laurence, K. M. Elias, and J. J. O'Shea IL-21 Is Produced by Th17 Cells and Drives IL-17 Production in a STAT3-dependent Manner J. Biol. Chem., November 30, 2007; 282(48): 34605 - 34610. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hiromura, T. Kishida, H. Nakano, T. Hama, J. Imanishi, Y. Hisa, and O. Mazda IL-21 Administration into the Nostril Alleviates Murine Allergic Rhinitis J. Immunol., November 15, 2007; 179(10): 7157 - 7165. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Ostiguy, E.-L. Allard, M. Marquis, J. Leignadier, and N. Labrecque IL-21 promotes T lymphocyte survival by activating the phosphatidylinositol-3 kinase signaling cascade J. Leukoc. Biol., September 1, 2007; 82(3): 645 - 656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chen, G. P. Sims, X. X. Chen, Y. Y. Gu, S. Chen, and P. E. Lipsky Modulatory Effects of 1,25-Dihydroxyvitamin D3 on Human B Cell Differentiation J. Immunol., August 1, 2007; 179(3): 1634 - 1647. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Hoffmann, W. Bayer, T. Grunwald, and O. Wildner Intratumoral expression of respiratory syncytial virus fusion protein in combination with cytokines encoded by adenoviral vectors as in situ tumor vaccine for colorectal cancer Mol. Cancer Ther., July 1, 2007; 6(7): 1942 - 1950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Withers, C. Fiorini, R. T. Fischer, R. Ettinger, P. E. Lipsky, and A. C. Grammer T cell dependent survival of CD20+ and CD20 plasma cells in human secondary lymphoid tissue Blood, June 1, 2007; 109(11): 4856 - 4864. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Zeng, R. Spolski, E. Casas, W. Zhu, D. E. Levy, and W. J. Leonard The molecular basis of IL-21-mediated proliferation Blood, May 15, 2007; 109(10): 4135 - 4142. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Metenou, A. L. Suguitan Jr., C. Long, R. G. F. Leke, and D. W. Taylor Fetal Immune Responses to Plasmodium falciparum Antigens in a Malaria-Endemic Region of Cameroon J. Immunol., March 1, 2007; 178(5): 2770 - 2777. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Frohlich, B. J. Marsland, I. Sonderegger, M. Kurrer, M. R. Hodge, N. L. Harris, and M. Kopf IL-21 receptor signaling is integral to the development of Th2 effector responses in vivo Blood, March 1, 2007; 109(5): 2023 - 2031. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Huggins, T. Pellegrin, R. E. Felgar, C. Wei, M. Brown, B. Zheng, E. C. B. Milner, S. H. Bernstein, I. Sanz, and M. S. Zand CpG DNA activation and plasma-cell differentiation of CD27- naive human B cells Blood, February 15, 2007; 109(4): 1611 - 1619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Konforte and C. J. Paige Identification of Cellular Intermediates and Molecular Pathways Induced by IL-21 in Human B Cells J. Immunol., December 15, 2006; 177(12): 8381 - 8392. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Jin and T. R. Malek Redundant and unique regulation of activated mouse B lymphocytes by IL-4 and IL-21 J. Leukoc. Biol., December 1, 2006; 80(6): 1416 - 1423. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Pene, L. Guglielmi, J.-F. Gauchat, N. Harrer, M. Woisetschlager, V. Boulay, J.-M. Fabre, P. Demoly, and H. Yssel IFN-{gamma}-Mediated Inhibition of Human IgE Synthesis by IL-21 Is Associated with a Polymorphism in the IL-21R Gene J. Immunol., October 15, 2006; 177(8): 5006 - 5013. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Good, V. L. Bryant, and S. G. Tangye Kinetics of Human B Cell Behavior and Amplification of Proliferative Responses following Stimulation with IL-21 J. Immunol., October 15, 2006; 177(8): 5236 - 5247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Jahrsdorfer, S. E. Blackwell, J. E. Wooldridge, J. Huang, M. W. Andreski, L. S. Jacobus, C. M. Taylor, and G. J. Weiner B-chronic lymphocytic leukemia cells and other B cells can produce granzyme B and gain cytotoxic potential after interleukin-21-based activation Blood, October 15, 2006; 108(8): 2712 - 2719. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
