| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Section of Immunobiology and
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520
A conventional view of the pathogenesis of systemic lupus erythematosus has emerged. The role of B cells is to secrete pathogenic autoantibodies, while the role of T cells is to provide help for autoantibody-producing B cells. A problem with this view is that spontaneous T cell activation as well as T cell infiltration of organs such as kidney and skin are prominent features in systemic lupus erythematosus patients and murine models of lupus. The identification of T cell infiltrates, in particular, suggests that autoantibody-mediated damage may be only part of the story and that T cells could also play a primary role in immune-mediated pathology. To test the role of B cells directly, we previously generated autoimmune-prone MRL-lpr/lpr mice that lack B cells. The complete absence of T cell infiltrates in these mice was surprising, and it prompted us to examine whether a key role of B cells in disease evolution is to prime autoreactive T cells. Here we demonstrate, by comparing B cell-deficient and control mice, that the expansion of activated and memory T cells in the MRL-lpr/lpr mouse is indeed highly dependent on B cells. These results suggest a novel role for B cells in autoimmune disregulation.
This article has been cited by other articles:
|
|
 |
|
  E. S. Mortensen and O. P. Rekvig Nephritogenic Potential of Anti-DNA Antibodies against Necrotic Nucleosomes J. Am. Soc. Nephrol., April 1, 2009; 20(4): 696 - 704. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. A. Gupta, M. L. Hermiston, G. Cassafer, D. I. Daikh, and A. Weiss B cells drive lymphocyte activation and expansion in mice with the CD45 wedge mutation and Fas deficiency J. Exp. Med., November 24, 2008; 205(12): 2755 - 2761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Ding, L. Wang, J. Marroquin, and J. Yan Targeting of antigens to B cells augments antigen-specific T-cell responses and breaks immune tolerance to tumor-associated antigen MUC1 Blood, October 1, 2008; 112(7): 2817 - 2825. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. P. Harvey, T. E. Quan, B. J. Rudenga, R. M. Roman, J. Craft, and M. J. Mamula Editing Antigen Presentation: Antigen Transfer between Human B Lymphocytes and Macrophages Mediated by Class A Scavenger Receptors J. Immunol., September 15, 2008; 181(6): 4043 - 4051. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Gavanescu, C. Benoist, and D. Mathis B cells are required for Aire-deficient mice to develop multi-organ autoinflammation: A therapeutic approach for APECED patients PNAS, September 2, 2008; 105(35): 13009 - 13014. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Li, F. Chen, M. Putt, Y. K. Koo, M. Madaio, J. C. Cambier, P. L. Cohen, and R. A. Eisenberg B Cell Depletion with Anti-CD79 mAbs Ameliorates Autoimmune Disease in MRL/lpr Mice J. Immunol., September 1, 2008; 181(5): 2961 - 2972. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kobayashi, K. Takahashi, Y. Nagai, T. Shibata, M. Otani, S. Izui, S. Akira, Y. Gotoh, H. Kiyono, and K. Miyake Tonic B cell activation by Radioprotective105/MD-1 promotes disease progression in MRL/lpr mice Int. Immunol., July 1, 2008; 20(7): 881 - 891. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. O'Neill, Y. Cao, K. M. Hamel, P. D. Doodes, G. Hutas, and A. Finnegan Expression of CD80/86 on B Cells Is Essential for Autoreactive T Cell Activation and the Development of Arthritis J. Immunol., October 15, 2007; 179(8): 5109 - 5116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ahuja, J. Shupe, R. Dunn, M. Kashgarian, M. R. Kehry, and M. J. Shlomchik Depletion of B Cells in Murine Lupus: Efficacy and Resistance J. Immunol., September 1, 2007; 179(5): 3351 - 3361. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Jiang, J. Foley, N. Clayton, G. Kissling, M. Jokinen, R. Herbert, and M. Diaz Abrogation of Lupus Nephritis in Activation-Induced Deaminase-Deficient MRL/lpr Mice J. Immunol., June 1, 2007; 178(11): 7422 - 7431. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Duddy, M. Niino, F. Adatia, S. Hebert, M. Freedman, H. Atkins, H. J. Kim, and A. Bar-Or Distinct Effector Cytokine Profiles of Memory and Naive Human B Cell Subsets and Implication in Multiple Sclerosis J. Immunol., May 15, 2007; 178(10): 6092 - 6099. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Herber, T. P. Brown, S. Liang, D. A. Young, M. Collins, and K. Dunussi-Joannopoulos IL-21 Has a Pathogenic Role in a Lupus-Prone Mouse Model and Its Blockade with IL-21R.Fc Reduces Disease Progression J. Immunol., March 15, 2007; 178(6): 3822 - 3830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yan, B. P. Harvey, R. J. Gee, M. J. Shlomchik, and M. J. Mamula B Cells Drive Early T Cell Autoimmunity In Vivo prior to Dendritic Cell-Mediated Autoantigen Presentation J. Immunol., October 1, 2006; 177(7): 4481 - 4487. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. O. Jacob, L. Pricop, C. Putterman, M. N. Koss, Y. Liu, M. Kollaros, S. A. Bixler, C. M. Ambrose, M. L. Scott, and W. Stohl Paucity of Clinical Disease despite Serological Autoimmunity and Kidney Pathology in Lupus-Prone New Zealand Mixed 2328 Mice Deficient in BAFF J. Immunol., August 15, 2006; 177(4): 2671 - 2680. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kalaaji, E. Mortensen, L. Jorgensen, R. Olsen, and O. P. Rekvig Nephritogenic Lupus Antibodies Recognize Glomerular Basement Membrane-Associated Chromatin Fragments Released from Apoptotic Intraglomerular Cells Am. J. Pathol., June 1, 2006; 168(6): 1779 - 1792. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Bonardelle, K. Benihoud, N. Kiger, and P. Bobe B lymphocytes mediate Fas-dependent cytotoxicity in MRL/lpr mice J. Leukoc. Biol., November 1, 2005; 78(5): 1052 - 1059. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yan, M. J. Wolff, J. Unternaehrer, I. Mellman, and M. J. Mamula Targeting antigen to CD19 on B cells efficiently activates T cells Int. Immunol., July 1, 2005; 17(7): 869 - 877. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Zielinski, S. N. Jacob, F. Bouzahzah, B. E. Ehrlich, and J. Craft Naive CD4+ T Cells from Lupus-Prone Fas-Intact MRL Mice Display TCR-Mediated Hyperproliferation Due to Intrinsic Threshold Defects in Activation J. Immunol., April 15, 2005; 174(8): 5100 - 5109. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. O'Neill, M. J. Shlomchik, T. T. Glant, Y. Cao, P. D. Doodes, and A. Finnegan Antigen-Specific B Cells Are Required as APCs and Autoantibody-Producing Cells for Induction of Severe Autoimmune Arthritis J. Immunol., March 15, 2005; 174(6): 3781 - 3788. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Lawman, C. Mauri, E. C. Jury, H. T. Cook, and M. R. Ehrenstein Atorvastatin Inhibits Autoreactive B Cell Activation and Delays Lupus Development in New Zealand Black/White F1 Mice J. Immunol., December 15, 2004; 173(12): 7641 - 7646. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R J Looney, J Anolik, and I Sanz B lymphocytes in systemic lupus erythematosus: lessons from therapy targeting B cells Lupus, May 1, 2004; 13(5): 381 - 390. [Abstract] [PDF]
|
|
|
|
|
|
N.-H. Chang, R. MacLeod, and J. E. Wither Autoreactive B Cells in Lupus-Prone New Zealand Black Mice Exhibit Aberrant Survival and Proliferation in the Presence of Self-Antigen In Vivo J. Immunol., February 1, 2004; 172(3): 1553 - 1560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Seagal, N. Leider, G. Wildbaum, N. Karin, and D. Melamed Increased plasma cell frequency and accumulation of abnormal syndecan-1plus T-cells in Ig{micro}-deficient/lpr mice Int. Immunol., September 1, 2003; 15(9): 1045 - 1052. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Wither, G. Lajoie, S. Heinrichs, Y.-C. Cai, N. Chang, A. Ciofani, Y.-H. Cheung, and R. MacLeod Functional Dissection of Lupus Susceptibility Loci on the New Zealand Black Mouse Chromosome 1: Evidence for Independent Genetic Loci Affecting T and B Cell Activation J. Immunol., August 15, 2003; 171(4): 1697 - 1706. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Catterall, D. Stockwell, V. Marshall, A. Strasser, and J. Allison Autoimmune kidney disease and lymphadenopathy in NODlpr mice are not modified by deficiency in tumor necrosis factor receptor 1 or {beta}2-microglobulin Int. Immunol., June 1, 2003; 15(6): 679 - 690. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Bouzahzah, S. Jung, and J. Craft CD4+ T Cells from Lupus-Prone Mice Avoid Antigen-Specific Tolerance Induction In Vivo J. Immunol., January 15, 2003; 170(2): 741 - 748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Li, H. Li, D. Ni, and M. Weigert Anti-DNA B Cells in MRL/lpr Mice Show Altered Differentiation and Editing Pattern J. Exp. Med., December 16, 2002; 196(12): 1543 - 1552. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R J Looney Treating human autoimmune disease by depleting B cells Ann Rheum Dis, October 1, 2002; 61(10): 863 - 866. [Full Text] [PDF]
|
|
|
|
|
|
E. S. Sobel, M. Satoh, Y. Chen, E. K. Wakeland, and L. Morel The Major Murine Systemic Lupus Erythematosus Susceptibility Locus Sle1 Results in Abnormal Functions of Both B and T Cells J. Immunol., September 1, 2002; 169(5): 2694 - 2700. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yan and M. J. Mamula B and T cell tolerance and autoimmunity in autoantibody transgenic mice Int. Immunol., August 1, 2002; 14(8): 963 - 971. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Trimble, K. A. Prince, G. A. Pestano, J. Daley, and H. Cantor Fas-Dependent Elimination of Nonselected CD8 Cells and lpr Disease J. Immunol., May 15, 2002; 168(10): 4960 - 4967. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yan and M. J. Mamula Autoreactive T Cells Revealed in the Normal Repertoire: Escape from Negative Selection and Peripheral Tolerance J. Immunol., April 1, 2002; 168(7): 3188 - 3194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Wang, W. Huang, M. Mihara, J. Sinha, and A. Davidson Mechanism of Action of Combined Short-Term CTLA4Ig and Anti-CD40 Ligand in Murine Systemic Lupus Erythematosus J. Immunol., February 15, 2002; 168(4): 2046 - 2053. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. P. L. Chiu, A. M. Jevnikar, and J. S. Danska Genetic Control of T and B Lymphocyte Activation in Nonobese Diabetic Mice J. Immunol., December 15, 2001; 167(12): 7169 - 7179. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Wellmann, M. Letz, A. Schneider, K. Amann, and T. H. Winkler An Ig {micro}-heavy chain transgene inhibits systemic lupus erythematosus immunopathology in autoimmune (NZB x NZW)F1 mice Int. Immunol., December 1, 2001; 13(12): 1461 - 1469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Rivera, C.-C. Chen, N. Ron, J. P. Dougherty, and Y. Ron Role of B cells as antigen-presenting cells in vivo revisited: antigen-specific B cells are essential for T cell expansion in lymph nodes and for systemic T cell responses to low antigen concentrations Int. Immunol., December 1, 2001; 13(12): 1583 - 1593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Liu, B. E. Anderson, M. E. Robert, J. M. McNiff, S. G. Emerson, W. D. Shlomchik, and M. J. Shlomchik Selective T-cell subset ablation demonstrates a role for T1 and T2 cells in ongoing acute graft-versus-host disease: a model system for the reversal of disease Blood, December 1, 2001; 98(12): 3367 - 3375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Takemura, P. A. Klimiuk, A. Braun, J. J. Goronzy, and C. M. Weyand T Cell Activation in Rheumatoid Synovium Is B Cell Dependent J. Immunol., October 15, 2001; 167(8): 4710 - 4718. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Fields, C. L. Sokol, A. Eaton-Bassiri, S.-j. Seo, M. P. Madaio, and J. Erikson Fas/Fas Ligand Deficiency Results in Altered Localization of Anti-Double-Stranded DNA B Cells and Dendritic Cells J. Immunol., August 15, 2001; 167(4): 2370 - 2378. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Shiokawa, N Matsumoto, and J Nishimura Clonal analysis of B cells in the osteoarthritis synovium Ann Rheum Dis, August 1, 2001; 60(8): 802 - 805. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W Kolowos, U S Gaipl, R E Voll, C Frank, J P Haas, T D Beyer, J R Kalden, and M Herrmann CD4 positive peripheral T cells from patients with systemic lupus erythematosus (SLE) are clonally expanded Lupus, May 1, 2001; 10(5): 321 - 331. [Abstract] [PDF]
|
|
|
|
|
|
D. Neumann, E. Del Giudice, A. Ciaramella, D. Boraschi, and P. Bossu Lymphocytes from Autoimmune MRL lpr/lpr Mice Are Hyperresponsive to IL-18 and Overexpress the IL-18 Receptor Accessory Chain J. Immunol., March 15, 2001; 166(6): 3757 - 3762. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Braley-Mullen and S. Yu Early Requirement for B Cells for Development of Spontaneous Autoimmune Thyroiditis in NOD.H-2h4 Mice J. Immunol., December 15, 2000; 165(12): 7262 - 7269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yi, M. McNerney, and S. K. Datta Regulatory Defects in Cbl and Mitogen-Activated Protein Kinase (Extracellular Signal-Related Kinase) Pathways Cause Persistent Hyperexpression of CD40 Ligand in Human Lupus T Cells J. Immunol., December 1, 2000; 165(11): 6627 - 6634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Melamed, E. Miri, N. Leider, and D. Nemazee Unexpected Autoantibody Production in Membrane Ig-{micro}-Deficient/lpr Mice J. Immunol., October 15, 2000; 165(8): 4353 - 4358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Freed, A. Marrs, J. VanderWall, P. L. Cohen, and R. A. Eisenberg MHC Class II-Bound Self Peptides from Autoimmune MRL/lpr Mice Reveal Potential T Cell Epitopes for Autoantibody Production in Murine Systemic Lupus Erythematosus J. Immunol., May 1, 2000; 164(9): 4697 - 4705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. T. M. Chan and M. J. Shlomchik Cutting Edge: B Cells Promote CD8+ T Cell Activation in MRL-Faslpr Mice Independently of MHC Class I Antigen Presentation J. Immunol., February 15, 2000; 164(4): 1658 - 1662. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Feuerstein, F. Chen, M. Madaio, M. Maldonado, and R. A. Eisenberg Induction of Autoimmunity in a Transgenic Model of B Cell Receptor Peripheral Tolerance: Changes in Coreceptors and B Cell Receptor-Induced Tyrosine-Phosphoproteins J. Immunol., November 15, 1999; 163(10): 5287 - 5297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. T. M. Chan, M. P. Madaio, and M. J. Shlomchik B Cells Are Required for Lupus Nephritis in the Polygenic, Fas-Intact MRL Model of Systemic Autoimmunity J. Immunol., October 1, 1999; 163(7): 3592 - 3596. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wang and M. J. Shlomchik Autoantigen-specific B Cell Activation in Fas-deficient Rheumatoid Factor Immunoglobulin Transgenic Mice J. Exp. Med., September 6, 1999; 190(5): 639 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Brard, M. Shannon, E. L. Prak, S. Litwin, and M. Weigert Somatic Mutation and Light Chain Rearrangement Generate Autoimmunity in Anti–single-stranded DNA Transgenic MRL/lpr Mice J. Exp. Med., September 6, 1999; 190(5): 691 - 704. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Liang, R. J. Gee, M. J. Kashgarian, A. H. Sharpe, and M. J. Mamula B7 Costimulation in the Development of Lupus: Autoimmunity Arises Either in the Absence of B7.1/B7.2 or in the Presence of Anti-B7.1/B7.2 Blocking Antibodies J. Immunol., August 15, 1999; 163(4): 2322 - 2329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Seery, E. C. Y. Wang, V. Cattell, J. M. Carroll, M. J. Owen, and F. M. Watt A Central Role for {alpha}{beta} T Cells in the Pathogenesis of Murine Lupus J. Immunol., June 15, 1999; 162(12): 7241 - 7248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Mandik-Nayak, S.-j. Seo, C. Sokol, K. M. Potts, A. Bui, and J. Erikson MRL-lpr/lpr Mice Exhibit a Defect in Maintaining Developmental Arrest and Follicular Exclusion of Anti-double-stranded DNA B Cells J. Exp. Med., June 7, 1999; 189(11): 1799 - 1814. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Maldonado, V. Kakkanaiah, G. C. MacDonald, F. Chen, E. A. Reap, E. Balish, W. R. Farkas, J. C. Jennette, M. P. Madaio, B. L. Kotzin, et al. The Role of Environmental Antigens in the Spontaneous Development of Autoimmunity in MRL-lpr Mice J. Immunol., June 1, 1999; 162(11): 6322 - 6330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. T.M. Chan, L. G. Hannum, A. M. Haberman, M. P. Madaio, and M. J. Shlomchik A Novel Mouse with B Cells but Lacking Serum Antibody Reveals an Antibody-independent Role for B Cells in Murine Lupus J. Exp. Med., May 17, 1999; 189(10): 1639 - 1648. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kaliyaperumal, M. A. Michaels, and S. K. Datta Antigen-Specific Therapy of Murine Lupus Nephritis Using Nucleosomal Peptides: Tolerance Spreading Impairs Pathogenic Function of Autoimmune T and B Cells J. Immunol., May 15, 1999; 162(10): 5775 - 5783. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S K Datta Production of pathogenic antibodies: Cognate interactions between autoimmune T and B cells Lupus, November 1, 1998; 7(9): 591 - 596. [Abstract] [PDF]
|
|
|
|
|
|
J. A. Kench, D. M. Russell, and D. Nemazee Efficient Peripheral Clonal Elimination of B Lymphocytes in MRL/lpr Mice Bearing Autoantibody Transgenes J. Exp. Med., September 7, 1998; 188(5): 909 - 917. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
