The role of B cells in lpr/lpr-induced autoimmunity

doi:10.1084/jem.180.4.1295

This Article

	Full Text (PDF)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Shlomchik, M. J.
	Articles by Huszar, D.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Shlomchik, M. J.
	Articles by Huszar, D.


Social Bookmarking

	What's this?

ARTICLES

The role of B cells in lpr/lpr-induced autoimmunity

MJ Shlomchik, MP Madaio, D Ni, M Trounstein and D Huszar
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.

The primary roles of T cells and B cells in the initiation of systemic autoimmunity are unclear. To investigate the role of B cells, we crossed the "Jh knockout" mutation onto the autoimmune lpr/lpr background. Animals homozygous for both traits were obtained. As expected, these animals lack B cells. These animals also show no signs of autoimmune kidney destruction nor vasculitis, in spite of carrying the lpr/lpr mutation. In contrast, lpr/lpr littermates that had B cells had severe nephritis and vasculitis, as well as autoantibodies. These results demonstrate a primary role for B cells and/or (auto)antibodies in initiating several types of autoimmune-mediated tissue destruction. The implications of this finding for models and therapy of autoimmunity are discussed.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Li, Y., Chen, F., Putt, M., Koo, Y. K., Madaio, M., Cambier, J. C., Cohen, P. L., Eisenberg, R. A. (2008). B Cell Depletion with Anti-CD79 mAbs Ameliorates Autoimmune Disease in MRL/lpr Mice. J. Immunol. 181: 2961-2972 [Abstract] [Full Text]
Kobayashi, T., Takahashi, K., Nagai, Y., Shibata, T., Otani, M., Izui, S., Akira, S., Gotoh, Y., Kiyono, H., Miyake, K. (2008). Tonic B cell activation by Radioprotective105/MD-1 promotes disease progression in MRL/lpr mice. Int Immunol 20: 881-891 [Abstract] [Full Text]
Tamimoto, Y., Horiuchi, T., Tsukamoto, H., Otsuka, J., Mitoma, H., Kimoto, Y., Nakashima, H., Muta, K., Abe, Y., Kiyohara, C., Ueda, A., Nagasawa, K., Yoshizawa, S., Shimoda, T., Harada, M. (2008). A dose-escalation study of rituximab for treatment of systemic lupus erythematosus and Evans' syndrome: immunological analysis of B cells, T cells and cytokines. Rheumatology (Oxford) 47: 821-827 [Abstract] [Full Text]
Saadoun, D., Rosenzwajg, M., Landau, D., Piette, J. C., Klatzmann, D., Cacoub, P. (2008). Restoration of peripheral immune homeostasis after rituximab in mixed cryoglobulinemia vasculitis. Blood 111: 5334-5341 [Abstract] [Full Text]
Brownlie, R. J., Lawlor, K. E., Niederer, H. A., Cutler, A. J., Xiang, Z., Clatworthy, M. R., Floto, R. A., Greaves, D. R., Lyons, P. A., Smith, K. G.C. (2008). Distinct cell-specific control of autoimmunity and infection by Fc{gamma}RIIb. J. Exp. Med. 205: 883-895 [Abstract] [Full Text]
Hamel, K., Doodes, P., Cao, Y., Wang, Y., Martinson, J., Dunn, R., Kehry, M. R., Farkas, B., Finnegan, A. (2008). Suppression of Proteoglycan-Induced Arthritis by Anti-CD20 B Cell Depletion Therapy Is Mediated by Reduction in Autoantibodies and CD4+ T Cell Reactivity. J. Immunol. 180: 4994-5003 [Abstract] [Full Text]
Ahuja, A., Shupe, J., Dunn, R., Kashgarian, M., Kehry, M. R., Shlomchik, M. J. (2007). Depletion of B Cells in Murine Lupus: Efficacy and Resistance. J. Immunol. 179: 3351-3361 [Abstract] [Full Text]
Jiang, C., Foley, J., Clayton, N., Kissling, G., Jokinen, M., Herbert, R., Diaz, M. (2007). Abrogation of Lupus Nephritis in Activation-Induced Deaminase-Deficient MRL/lpr Mice. J. Immunol. 178: 7422-7431 [Abstract] [Full Text]
Toubi, E, Kessel, A, Slobodin, G, Boulman, N, Pavlotzky, E, Zisman, D, Rozenbaum, M, Rosner, I (2007). Changes in macrophage function after rituximab treatment in patients with rheumatoid arthritis. Ann Rheum Dis 66: 818-820 [Abstract] [Full Text]
Herber, D., Brown, T. P., Liang, S., Young, D. A., Collins, M., Dunussi-Joannopoulos, K. (2007). IL-21 Has a Pathogenic Role in a Lupus-Prone Mouse Model and Its Blockade with IL-21R.Fc Reduces Disease Progression. J. Immunol. 178: 3822-3830 [Abstract] [Full Text]
Kumazaki, K., Tirosh, B., Maehr, R., Boes, M., Honjo, T., Ploegh, H. L. (2007). AID-/-{micro}s-/- Mice Are Agammaglobulinemic and Fail to Maintain B220-CD138+ Plasma Cells. J. Immunol. 178: 2192-2203 [Abstract] [Full Text]
Ma, Z., Chen, F., Madaio, M. P., Cohen, P. L., Eisenberg, R. A. (2006). Modulation of Autoimmunity by TLR9 in the Chronic Graft-vs-Host Model of Systemic Lupus Erythematosus. J. Immunol. 177: 7444-7450 [Abstract] [Full Text]
Yan, J., Harvey, B. P., Gee, R. J., Shlomchik, M. J., Mamula, M. J. (2006). B Cells Drive Early T Cell Autoimmunity In Vivo prior to Dendritic Cell-Mediated Autoantigen Presentation. J. Immunol. 177: 4481-4487 [Abstract] [Full Text]
Jacob, C. O., Pricop, L., Putterman, C., Koss, M. N., Liu, Y., Kollaros, M., Bixler, S. A., Ambrose, C. M., Scott, M. L., Stohl, W. (2006). Paucity of Clinical Disease despite Serological Autoimmunity and Kidney Pathology in Lupus-Prone New Zealand Mixed 2328 Mice Deficient in BAFF. J. Immunol. 177: 2671-2680 [Abstract] [Full Text]
Zeller, G. C., Hirahashi, J., Schwarting, A., Sharpe, A. H., Kelley, V. R. (2006). Inducible Co-Stimulator Null MRL-Faslpr Mice: Uncoupling of Autoantibodies and T Cell Responses in Lupus. J. Am. Soc. Nephrol. 17: 122-130 [Abstract] [Full Text]
Bonardelle, D., Benihoud, K., Kiger, N., Bobe, P. (2005). B lymphocytes mediate Fas-dependent cytotoxicity in MRL/lpr mice. J. Leukoc. Biol. 78: 1052-1059 [Abstract] [Full Text]
Clark, E A, Ledbetter, J A (2005). How does B cell depletion therapy work, and how can it be improved?. Ann Rheum Dis 64: iv77-iv80 [Abstract] [Full Text]
Christensen, S. R., Kashgarian, M., Alexopoulou, L., Flavell, R. A., Akira, S., Shlomchik, M. J. (2005). Toll-like receptor 9 controls anti-DNA autoantibody production in murine lupus. J. Exp. Med. 202: 321-331 [Abstract] [Full Text]
O'Neill, S. K., Shlomchik, M. J., Glant, T. T., Cao, Y., Doodes, P. D., Finnegan, A. (2005). Antigen-Specific B Cells Are Required as APCs and Autoantibody-Producing Cells for Induction of Severe Autoimmune Arthritis. J. Immunol. 174: 3781-3788 [Abstract] [Full Text]
Chambers, S A, Isenberg, D (2005). Anti-B cell therapy (Rituximab) in the treatment of autoimmune diseases. Lupus 14: 210-214 [Abstract]
Edwards, J. C. W., Cambridge, G. (2005). Prospects for B-cell-targeted therapy in autoimmune disease. Rheumatology (Oxford) 44: 151-156 [Full Text]
Lenda, D. M., Stanley, E. R., Kelley, V. R. (2004). Negative Role of Colony-Stimulating Factor-1 in Macrophage, T Cell, and B Cell Mediated Autoimmune Disease in MRL-Faslpr Mice. J. Immunol. 173: 4744-4754 [Abstract] [Full Text]
Reilly, C. M., Mishra, N., Miller, J. M., Joshi, D., Ruiz, P., Richon, V. M., Marks, P. A., Gilkeson, G. S. (2004). Modulation of Renal Disease in MRL/lpr Mice by Suberoylanilide Hydroxamic Acid. J. Immunol. 173: 4171-4178 [Abstract] [Full Text]
Hao, Z., Hampel, B., Yagita, H., Rajewsky, K. (2004). T Cell-specific Ablation of Fas Leads to Fas Ligand-mediated Lymphocyte Depletion and Inflammatory Pulmonary Fibrosis. J. Exp. Med. 199: 1355-1365 [Abstract] [Full Text]
Robey, I. F., Peterson, M., Horwitz, M. S., Kono, D. H., Stratmann, T., Theofilopoulos, A. N., Sarvetnick, N., Teyton, L., Feeney, A. J. (2004). Terminal Deoxynucleotidyltransferase Deficiency Decreases Autoimmune Disease in Diabetes-Prone Nonobese Diabetic Mice and Lupus-Prone MRL-Faslpr Mice. J. Immunol. 172: 4624-4629 [Abstract] [Full Text]
Sekine, H., Watanabe, H., Gilkeson, G. S. (2004). Enrichment of Anti-Glomerular Antigen Antibody-Producing Cells in the Kidneys of MRL/MpJ-Faslpr Mice. J. Immunol. 172: 3913-3921 [Abstract] [Full Text]
Xiao, S., Sung, S.-s. J., Fu, S. M., Ju, S.-T. (2003). Combining Fas Mutation with Interleukin-2 Deficiency Prevents Colitis and Lupus: IMPLICATING INTERLEUKIN-2 FOR AUTO-REACTIVE T CELL EXPANSION AND Fas LIGAND FOR COLON EPITHELIAL CELL DEATH. J. Biol. Chem. 278: 52730-52738 [Abstract] [Full Text]
Seagal, J., Leider, N., Wildbaum, G., Karin, N., Melamed, D. (2003). Increased plasma cell frequency and accumulation of abnormal syndecan-1plus T-cells in Ig{micro}-deficient/lpr mice. Int Immunol 15: 1045-1052 [Abstract] [Full Text]
Catterall, T., Stockwell, D., Marshall, V., Strasser, A., Allison, J. (2003). 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 15: 679-690 [Abstract] [Full Text]
Looney, R J (2002). Treating human autoimmune disease by depleting B cells. Ann Rheum Dis 61: 863-866 [Full Text]
Miwa, T., Maldonado, M. A., Zhou, L., Sun, X., Luo, H. Y., Cai, D., Werth, V. P., Madaio, M. P., Eisenberg, R. A., Song, W.-C. (2002). Deletion of Decay-Accelerating Factor (CD55) Exacerbates Autoimmune Disease Development in MRL/lpr Mice. Am. J. Pathol. 161: 1077-1086 [Abstract] [Full Text]
Bloom, R. D., O'Connor, T., Cizman, B., Kalluri, R., Naji, A., Madaio, M. P. (2002). Intrathymic kidney cells delay the onset of lupus nephritis in MRL-lpr/lpr mice. Int Immunol 14: 867-871 [Abstract] [Full Text]
Trimble, L. A., Prince, K. A., Pestano, G. A., Daley, J., Cantor, H. (2002). Fas-Dependent Elimination of Nonselected CD8 Cells and lpr Disease. J. Immunol. 168: 4960-4967 [Abstract] [Full Text]
Peng, S. L., Szabo, S. J., Glimcher, L. H. (2002). T-bet regulates IgG class switching and pathogenic autoantibody production. Proc. Natl. Acad. Sci. USA 99: 5545-5550 [Abstract] [Full Text]
Sekiguchi, D. R., Jainandunsing, S. M., Fields, M. L., Maldonado, M. A., Madaio, M. P., Erikson, J., Weigert, M., Eisenberg, R. A. (2002). Chronic Graft-Versus-Host in Ig Knockin Transgenic Mice Abrogates B Cell Tolerance in Anti-Double-Stranded DNA B Cells. J. Immunol. 168: 4142-4153 [Abstract] [Full Text]
Yan, J., Mamula, M. J. (2002). Autoreactive T Cells Revealed in the Normal Repertoire: Escape from Negative Selection and Peripheral Tolerance. J. Immunol. 168: 3188-3194 [Abstract] [Full Text]
Chiu, P. P. L., Jevnikar, A. M., Danska, J. S. (2001). Genetic Control of T and B Lymphocyte Activation in Nonobese Diabetic Mice. J. Immunol. 167: 7169-7179 [Abstract] [Full Text]
Wellmann, U., Letz, M., Schneider, A., Amann, K., Winkler, T. H. (2001). An Ig {micro}-heavy chain transgene inhibits systemic lupus erythematosus immunopathology in autoimmune (NZB x NZW)F1 mice. Int Immunol 13: 1461-1469 [Abstract] [Full Text]
Rivera, A., Chen, C.-C., Ron, N., Dougherty, J. P., Ron, Y. (2001). 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 13: 1583-1593 [Abstract] [Full Text]
Arce, E., Jackson, D. G., Gill, M. A., Bennett, L. B., Banchereau, J., Pascual, V. (2001). Increased Frequency of Pre-germinal Center B Cells and Plasma Cell Precursors in the Blood of Children with Systemic Lupus Erythematosus. J. Immunol. 167: 2361-2369 [Abstract] [Full Text]
Melamed, D., Miri, E., Leider, N., Nemazee, D. (2000). Unexpected Autoantibody Production in Membrane Ig-{micro}-Deficient/lpr Mice. J. Immunol. 165: 4353-4358 [Abstract] [Full Text]
Stoll, M. L., Gavalchin, J. (2000). Systemic lupus erythematosus--messages from experimental models. Rheumatology (Oxford) 39: 18-27 [Full Text]
Feuerstein, N., Chen, F., Madaio, M., Maldonado, M., Eisenberg, R. A. (1999). 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. 163: 5287-5297 [Abstract] [Full Text]
Chan, O. T. M., Madaio, M. P., Shlomchik, M. J. (1999). B Cells Are Required for Lupus Nephritis in the Polygenic, Fas-Intact MRL Model of Systemic Autoimmunity. J. Immunol. 163: 3592-3596 [Abstract] [Full Text]
Tada, Y., Nagasawa, K., Ho, A., Morito, F., Koarada, S., Ushiyama, O., Suzuki, N., Ohta, A., Mak, T. W. (1999). Role of the Costimulatory Molecule CD28 in the Development of Lupus in MRL/lpr Mice. J. Immunol. 163: 3153-3159 [Abstract] [Full Text]
Shinde, S., Gee, R., Santulli-Marotto, S., Bockenstedt, L. K., Clarke, S. H., Mamula, M. J. (1999). T Cell Autoimmunity in Ig Transgenic Mice. J. Immunol. 162: 7519-7524 [Abstract] [Full Text]
Maldonado, M. A., Kakkanaiah, V., MacDonald, G. C., Chen, F., Reap, E. A., Balish, E., Farkas, W. R., Jennette, J. C., Madaio, M. P., Kotzin, B. L., Cohen, P. L., Eisenberg, R. A. (1999). The Role of Environmental Antigens in the Spontaneous Development of Autoimmunity in MRL-lpr Mice. J. Immunol. 162: 6322-6330 [Abstract] [Full Text]
Chan, O. T.M., Hannum, L. G., Haberman, A. M., Madaio, M. P., Shlomchik, M. J. (1999). A Novel Mouse with B Cells but Lacking Serum Antibody Reveals an Antibody-independent Role for B Cells in Murine Lupus. J. Exp. Med. 189: 1639-1648 [Abstract] [Full Text]
Chen, F., Maldonado, M. A., Madaio, M., Eisenberg, R. A. (1998). The Role of Host (Endogenous) T Cells in Chronic Graft-Versus-Host Autoimmune Disease. J. Immunol. 161: 5880-5885 [Abstract] [Full Text]
Theofilopoulos, A N (1998). Effector and predisposing genes in murine lupus. Lupus 7: 575-584 [Abstract]
Pewzner-Jung, Y., Friedmann, D., Sonoda, E., Jung, S., Rajewsky, K., Eilat, D. (1998). B Cell Deletion, Anergy, and Receptor Editing in ""Knock In"" Mice Targeted with a Germline-Encoded or Somatically Mutated Anti-DNA Heavy Chain. J. Immunol. 161: 4634-4645 [Abstract] [Full Text]
Kench, J. A., Russell, D. M., Nemazee, D. (1998). Efficient Peripheral Clonal Elimination of B Lymphocytes in MRL/lpr Mice Bearing Autoantibody Transgenes. J. Exp. Med. 188: 909-917 [Abstract] [Full Text]
Li, S., Kurts, C., Kontgen, F., Holdsworth, S. R., Tipping, P. G. (1998). Major Histocompatibility Complex Class II Expression by Intrinsic Renal Cells Is Required for Crescentic Glomerulonephritis. J. Exp. Med. 188: 597-602 [Abstract] [Full Text]
Russell, J. Q., Mooney, T., Cohen, P. L., MacPherson, B., Noelle, R. J., Budd, R. C. (1998). Anti-CD40L Accelerates Renal Disease and Adenopathy in MRL-lpr Mice in Parallel with Decreased Thymocyte Apoptosis. J. Immunol. 161: 729-739 [Abstract] [Full Text]
Macaulay, A. E., DeKruyff, R. H., Umetsu, D. T. (1998). Antigen-Primed T Cells from B Cell-Deficient JHD Mice Fail to Provide B Cell Help. J. Immunol. 160: 1694-1700 [Abstract] [Full Text]
Sobel, E. S., Kakkanaiah, V. N., Schiffenbauer, J., Reap, E. A., Cohen, P. L., Eisenberg, R. A. (1998). Novel Immunoregulatory B Cell Pathways Revealed by lpr-+ Mixed Chimeras. J. Immunol. 160: 1497-1503 [Abstract] [Full Text]
Peng, S. L., Moslehi, J., Robert, M. E., Craft, J. (1998). Perforin Protects Against Autoimmunity in Lupus-Prone Mice. J. Immunol. 160: 652-660 [Abstract] [Full Text]
Chan, O., J. Shlomchik, M. (1998). A New Role for B Cells in Systemic Autoimmunity: B Cells Promote Spontaneous T Cell Activation in MRL-lpr/lpr Mice. J. Immunol. 160: 51-59 [Abstract] [Full Text]