Article information
Resumen
El éxito del rituximab en el tratamiento de pacientes con artritis reumatoide (AR) ha favorecido la reevaluación del papel de los linfocitos B en la patogenia de esta enfermedad. En la membrana sinovial inflamada de pacientes con AR se observa una acumulación y expansión clonal de linfocitos B, formación ectópica de centros germinales, acumulación de células plasmáticas, producción local de autoanticuerpos y depósito de inmunocomplejos. Además, en modelos animals de artritis inflamatoria se ha demostrado que las células B son necesarias para que se produzca el daño mediado por linfocitos T. Todo ello indica que los linfocitos B son importantes en la patogenia de la AR. Varios estudios han demostrado que el contacto con fibroblastos sinoviales es esencial para la acumulación y la supervivencia de los linfocitos B en la articulación reumatoidea, así como para su diferenciación hacia células plasmáticas.
Palabras clave:
Artritis reumatoide
Linfocito B
inoviocito tipo fibroblasto
Abstract
The success of rituximab in the treatment of patients with RA has led investigators to reassess the role of B cells in RA pathogenesis. In the RA synovium there is B-lymphocyte accumulation and clonal expansion, formation of ectopic germinal centers, plasma cell accumulation, and deposits of immune complexes, suggesting that B cells and their products participate in disease progression. Moreover, a recently described animal model that simulates RA demonstrates a critical need for B cells in the transition of T-cell autoreactivity to immunoglobulin-mediated joint destruction. Prior in vitro studies of requirements for B-cell survival in the synovial membrane and local differentiation into plasma cells concluded that cell contact between synovial fibroblasts and B cells is essential.
Key words:
Rheumatoid arthritis
B lymphocyte
Fibroblastlike synoviocyte
Full text is only aviable in PDF
Bibliografía
[1.]
J.C. Edwards, L. Szczepanski, J. Szechinski, et al.
Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis.
N Engl J Med, 350 (2004), pp. 2572-2581
[2.]
J. Dechanet, P. Merville, I. Durand, et al.
The ability of synoviocytes to support terminal differentiation of activated B cells may explain plasma cell accumulation in rheumatoid synovium.
J Clin Invest, 95 (1995), pp. 456-463
[3.]
S. Takemura, P.A. Klimiuk, A. Braun, et al.
T cell activation in rheumatoid synovium is B cell dependent.
J Immunol, 167 (2001), pp. 4710-4718
[4.]
N.J. Zvaifler, D. Boyle, G.S. Firestein.
Early synovitis-synoviocytes and mononuclear cells.
Semin Arthritis Rheum, 23 (1994), pp. 11-16
[5.]
M. Feldmann, F.M. Brennan, R.N. Maini.
Role of cytokines in rheumatoid arthritis.
Ann Rev Immunol, 14 (1996), pp. 397-440
[6.]
R.W. Kinne, R. Brauer, B. Stuhlmuller, et al.
Macrophages in rheumatoid arthritis.
Arthritis Res, 2 (2000), pp. 189-202
[7.]
G.S. Firestein, N.J. Zvaifler.
Peripheral blood and synovial fluid monocyte activation in inflammatory arthritis. I. A cytofluorographic study of monocyte differentiation antigens and class II antigens and their regulation by gamma-interferon.
Arthritis Rheum, 30 (1987), pp. 857-863
[8.]
I.B. McInnes, F.Y. Liew.
Interleukin 15: a proinflammatory role in rheumatoid arthritis synovitis.
Immunol Today, 19 (1998), pp. 75-79
[9.]
C.M. Weyand, J.J. Goronzy.
Ectopic germinal center formation in rheumatoid synovitis.
Ann N Y Acad Sci, 987 (2003), pp. 140-149
[10.]
N.J. Zvaifler.
Rheumatoid synovitis. An extravascular immune complex disease.
Arthritis Rheum, 17 (1974), pp. 297-305
[11.]
T. Dorner, G.R. Burmester.
The role of B cells in rheumatoid arthritis: mechanisms and therapeutic targets.
Curr Opin Rheumatol, 15 (2003), pp. 246-252
[12.]
E. Lindhout, M. Van Eijk, M. Van Pel, et al.
Fibroblast-like synoviocytes from rheumatoid arthritis patients have intrinsic properties of follicular dendritic cells.
J Immunol, 162 (1999), pp. 5949-5956
[13.]
J.A. Burger, N.J. Zvaifler, N. Tsukada, et al.
Fibroblast-like synoviocytes support B-cell pseudoemperipolesis via a stromal cell-derived factor-1- and CD106 (VCAM-1)-dependent mechanism.
J Clin Invest, 107 (2001), pp. 305-315
[14.]
K. Shi, K. Hayashida, M. Kaneko, et al.
Lymphoid chemokine B cell-attracting chemokine-1 (CXCL13) is expressed in germinal center of ectopic lymphoid follicles within the synovium of chronic arthritis patients.
J Immunol, 166 (2001), pp. 650-655
[15.]
S. Takemura, A. Braun, C. Crowson, et al.
Lymphoid neogenesis in rheumatoid synovitis.
J Immunol, 167 (2001), pp. 1072-1080
[16.]
J. Morales-Ducret, E. Wayner, M.J. Elices, et al.
Alpha 4/beta 1 integrin (VLA-4) ligands in arthritis. Vascular cell adhesion molecule-1 expression in synovium and on fibroblast-like synoviocytes.
J Immunol, 149 (1992), pp. 1424-1431
[17.]
J. Ohata, N.J. Zvaifler, M. Nishio, et al.
Fibroblast-like synoviocytes of mesenchymal origin express functional B cell-activating factor of the TNF family in response to proinflammatory cytokines.
J Immunol, 174 (2005), pp. 864-870
[18.]
A.N. Akbar, M. Salmon.
Cellular environments and apoptosis: tissue microenvironments control activated T-cell death.
Immunol Today, 18 (1997), pp. 72-76
[19.]
C.D. Buckley, D. Pilling, J.M. Lord, et al.
Fibroblasts regulate the switch from acute resolving to chronic persistent inflammation.
Trends Immunol, 22 (2001), pp. 199-204
[20.]
T. Komuro.
Re-evaluation of fibroblasts and fibroblast-like cells.
Anat. Embryol, 182 (1990), pp. 103-112
[21.]
J.J. Owen, D.E. McLoughlin, R.K. Suniara, et al.
The role of mesenchyme in thymus development.
Curr Top Microbiol Immunol, 251 (2000), pp. 133-137
[22.]
R.K. Suniara, E.J. Jenkinson, J.J. Owen.
An essential role for thymic mesenchyme in early T cell development.
J Exp Med, 191 (2000), pp. 1051-1056
[23.]
K.M. Fries, T. Blieden, R.J. Looney, et al.
Evidence of fibroblast heterogeneity and the role of fibroblast subpopulations in fibrosis.
Clin Immunol Immunopathol, 72 (1994), pp. 283-292
[24.]
D. Brouty-Boye, C. Pottin-Clemenceau, C. Doucet, et al.
Chemokines and CD40 expression in human fibroblasts.
Eur J Immunol, 30 (2000), pp. 914-919
[25.]
L. Marinova-Mutafchieva, P. Taylor, K. Funa, et al.
Mesenchymal cells expressing bone morphogenetic protein receptors are present in the rheumatoid arthritis joint.
Arthritis Rheum, 43 (2000), pp. 2046-2055
[26.]
J. Harris, et al.
Differentiated cells and the maintenance of tissues.
Molecular Biology of the Cell, pp. 1139-1193
[27.]
N.J. Zvaifler, L. Marinova-Mutafchieva, G. Adams, et al.
Mesenchymal precursor cells in the blood of normal individuals.
Arthritis Res, 2 (2000), pp. 477-488
[28.]
P. Bianco, P. Gehron Robey.
Marrow stromal stem cells.
J Clin Invest, 105 (2000), pp. 1663-1668
[29.]
A.D. Whetton, G.J. Graham.
Homing and mobilization in the stem cell niche.
Trends Cell Biol, 9 (1999), pp. 233-238
[30.]
G. Parsonage, F. Falciani, A. Burman, et al.
Global gene expression profiles in fibroblasts from synovial, skin and lymphoid tissue reveals distinct cytokine and chemokine expression patterns.
Thromb Haemost, 90 (2003), pp. 688-697
[31.]
H.Y. Chang, J.T. Chi, S. Dudoit, et al.
Diversity, topographic differentiation, and positional memory in human fibroblasts.
Proc Natl Acad Sci U S A, 99 (2002), pp. 12877-12882
[32.]
S.F. Gilbert.
The genetics of axis specification in Drosophila.
Developmental Biology, 4.a ed., pp. 531-574
[33.]
J.T. Chi, H.Y. Chang, G. Haraldsen, et al.
Endothelial cell diversity revealed by global expression profiling.
Proc Natl Acad Sci U S A, 100 (2003), pp. 10623-10628
[34.]
P. Oh, Y. Li, J. Yu, et al.
Subtractive proteomic mapping of the endothelial surface in lung and solid tumours for tissuespecific therapy.
Nature, 429 (2004), pp. 629-635
[35.]
S. Podgrabinska, P. Braun, P. Velasco, et al.
Molecular characterization of lymphatic endothelial cells.
Proc Natl Acad Sci U S A, 99 (2002), pp. 16069-16074
[36.]
T. Pap, U. Muller-Ladner, R.E. Gay, et al.
Fibroblast biology. Role of synovial fibroblasts in the pathogenesis of rheumatoid arthritis.
Arthritis Res, 2 (2000), pp. 361-367
[37.]
C.M. Hogaboam, C.L. Bone-Larson, S. Lipinski, et al.
Differential monocyte chemoattractant protein-1 and chemokine receptor 2 expression by murine lung fibroblasts derived from Th1- and Th2-type pulmonary granuloma models.
J Immunol, 163 (1999), pp. 2193-2201
[38.]
Z. Zhu, R.J. Homer, Z. Wang, et al.
Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production.
J Clin Invest, 103 (1999), pp. 779-788
[39.]
M.M. Hitt, J. Gauldie.
Gene vectors for cytokine expression in vivo.
Curr Pharm Des, 6 (2000), pp. 613-632
[40.]
A.V. Miagkov, D.V. Kovalenko, C.E. Brown, et al.
NF-kappaB activation provides the potential link between inflammation and hyperplasia in the arthritic joint.
Proc Natl Acad Sci U S A, 95 (1998), pp. 13859-13864
[41.]
R. Bucala, C. Ritchlin, R. Winchester, et al.
Constitutive production of inflammatory and mitogenic cytokines by rheumatoid synovial fibroblasts.
J Exp Med, 173 (1991), pp. 569-574
[42.]
T. Seki, J. Selby, T. Haupl, et al.
Use of differential subtraction method to identify genes that characterize the phenotype of cultured rheumatoid arthritis synoviocytes.
Arthritis Rheum, 41 (1998), pp. 1356-1364
[43.]
U. Müller-Ladner, J. Kriegsmann, B.N. Franklin, et al.
Synovial fibroblasts of patients with rheumatoid arthritis attach to and invade normal human cartilage when engrafted into SCID mice.
Am J Pathol, 5 (1996), pp. 1607
[44.]
Y. Shimaoka, J.F. Attrep, T. Hirano, et al.
Nurse-like cells from bone marrow and synovium of patients with rheumatoid arthritis promote survival and enhance function of human B cells.
J Clin Invest, 102 (1998), pp. 606-618
[45.]
I.C.M. MacLennan.
Germinal centers.
Ann Rev Immunol, 12 (1994), pp. 117-139
[46.]
J.C. Edwards, R.D. Leigh, G. Cambridge.
Expression of molecules involved in B lymphocyte survival and differentiation by synovial fibroblasts.
Clin Exp Immunol, 108 (1997), pp. 407-414
[47.]
I. Randen, O.J. Mellbye, O. Forre, et al.
The identification of germinal centres and follicular dendritic cell networks in rheumatoid synovial tissue.
Scand J Immunol, 41 (1995), pp. 481-486
[48.]
J.C. Edwards, L.S. Wilkinson, P. Speight, et al.
Vascular cell adhesion molecule 1 and alpha 4 and beta 1 integrins in lymphocyte aggregates in Sjogren's syndrome and rheumatoidarthritis.
Ann Rheum Dis, 52 (1993), pp. 806-811
[49.]
G.S. Firestein, et al.
Etiology of rheumatoid arthritis.
Textbook of Rheumatology, 5.a ed., pp. 851
[50.]
E. Lindhout, C. De Groot.
Follicular dendritic cells and apoptosis: life and death in the germinal center.
Histochem J, 27 (1995), pp. 167-183
[51.]
A. Villena, A. Zapata, J.M. Rivera-Pomar, et al.
Structure of the non-lymphoid cells during the postnatal development of the rat lymph nodes. Fibroblastic reticulum cells and interdigitating cells.
Cell Tissue Res, 229 (1983), pp. 219-232
[52.]
A. Cerny, R.M. Zinkernagel, P. Groscurth.
Development of follicular dendritic cells in lymph nodes of B-cell-depleted mice.
Cell Tissue Res, 254 (1988), pp. 449-454
[53.]
R. Abe, S.C. Donnelly, T. Peng, et al.
ipheral blood fibrocytes: differentiation pathway and migration to wound sites.
J Immunol, 166 (2001), pp. 7556-7562
[54.]
M. Sen, K. Lauterbach, H. El-Gabalawy, et al.
Expression and function of wingless and frizzled homologs in rheumatoid arthritis.
Proc Natl Acad Sci U S A, 97 (2000), pp. 2791-2796
[55.]
H. Wekerle, U.P. Ketelsen.
Thymic nurse cells: Ia-bearing epithelium involved in T-lymphocyte differentiation?.
Nature, 283 (1980), pp. 402-404
[56.]
R. Tsunoda, M. Nakayama, E. Heinen, et al.
Emperipolesis of lymphoid cells by human follicular dendritic cells in vitro.
Virchows Arch B Cell Pathol Incl Mol Pathol, 62 (1992), pp. 69-78
[57.]
E.A. Clark, K.H. Grabstein, G.L. Shu.
Cultured human follicular dendritic cells. Growth characteristics and interactions with B lymphocytes.
J Immunol, 148 (1992), pp. 3327-3335
[58.]
J.H. Humphrey, D. Grennan, V. Sundaram.
The origin of follicular dendritic cells in the mouse and the mechanism of trapping of immune complexes on them.
Eur J Immunol, 14 (1984), pp. 859-864
[59.]
F. Mackay, P. Schneider, P. Rennert, et al.
BAFF AND APRIL: a tutorial on B cell survival.
Ann Rev Immunol, 21 (2003), pp. 231-264
[60.]
H. Hase, Y. Kanno, M. Kojima, et al.
BAFF/BLyS can potentiate B-cell selection with the B-cell coreceptor complex.
Blood, 103 (2004), pp. 2257-2265
[61.]
S.M. Tan, D. Xu, V. Roschke, et al.
Local production of B lymphocyte stimulator protein and APRIL in arthritic joints of patients with inflammatory arthritis.
Arthritis Rheum, 48 (2003), pp. 982-992
[62.]
C.S. Goodyear, D.L. Boyle, G.J. Silverman.
Secretion of BAFF by fibroblast-like synoviocytes from rheumatoid arthritis biopsies attenuates B-cell depletion by rituximab.
Athritis Rheum, 52 (2005), pp. S290
Copyright © 2006. Sociedad Española de Reumatología