Cell-intrinsic expression of TLR9 in autoreactive B cells constrains BCR/TLR7-dependent responses

Journal of Immunology

Volumn 194, Issue 6, 2015, Pages 2504-2512

  Nündel, Kerstin ^a   Green, Nathaniel M ^a   Shaffer, Arthur L ^b   Moody, Krishna L ^a   Busto, Patricia ^a   Eilat, Dan ^c   Miyake, Kensuke ^d   Oropallo, Michael A ^e   Cancro, Michael P ^e   Marshak Rothstein, Ann ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^b NATIONAL CANCER INSTITUTE   (United States)

^c HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

^d UNIVERSITY OF TOKYO   (Japan)

^e UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

B LYMPHOCYTE RECEPTOR; INTERFERON CONSENSUS SEQUENCE BINDING PROTEIN; INTERFERON REGULATORY FACTOR 4; SYNDECAN 1; TOLL LIKE RECEPTOR 7; TOLL LIKE RECEPTOR 9; AUTOANTIBODY; AUTOANTIGEN; INTERFERON REGULATORY FACTOR; INTERFERON REGULATORY FACTOR-4; LYMPHOCYTE ANTIGEN RECEPTOR; RHEUMATOID FACTOR; TRANSCRIPTOME;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; B LYMPHOCYTE; B LYMPHOCYTE ACTIVATION; B LYMPHOCYTE DIFFERENTIATION; CELL LINEAGE; CELL SURVIVAL; CONTROLLED STUDY; IN VITRO STUDY; IN VIVO STUDY; LYMPHOCYTE PROLIFERATION; MOUSE; NONHUMAN; PLASMA CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; WILD TYPE; ANIMAL; AUTOIMMUNITY; BAGG ALBINO MOUSE; CELL CULTURE; CELL DIFFERENTIATION; CELL PROLIFERATION; DEFICIENCY; DNA MICROARRAY; FLOW CYTOMETRY; GENETICS; IMMUNOLOGY; KNOCKOUT MOUSE; LYMPHOCYTE ACTIVATION; METABOLISM; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TRANSGENIC MOUSE;

ANIMALS; AUTOANTIBODIES; AUTOANTIGENS; AUTOIMMUNITY; B-LYMPHOCYTES; CELL DIFFERENTIATION; CELL PROLIFERATION; CELLS, CULTURED; FLOW CYTOMETRY; INTERFERON REGULATORY FACTORS; LYMPHOCYTE ACTIVATION; MICE, INBRED BALB C; MICE, KNOCKOUT; MICE, TRANSGENIC; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; PLASMA CELLS; RECEPTORS, ANTIGEN, B-CELL; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RHEUMATOID FACTOR; SYNDECAN-1; TOLL-LIKE RECEPTOR 7; TOLL-LIKE RECEPTOR 9; TRANSCRIPTOME;

EID: 84924565569     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1402425     Document Type: Article

References (49)

1. Leadbetter, E. A., I. R. Rifkin, A. M. Hohlbaum, B. C. Beaudette, M. J. Shlomchik, and A. Marshak-Rothstein. 2002. Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors. Nature 416: 603-607.
2. Christensen, S. R., J. Shupe, K. Nickerson, M. Kashgarian, R. A. Flavell, and M. J. Shlomchik. 2006. Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine model of lupus. Immunity 25: 417-428.
3. Pisitkun, P., J. A. Deane, M. J. Difilippantonio, T. Tarasenko, A. B. Satterthwaite, and S. Bolland. 2006. Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication. Science 312: 1669-1672.
4. Subramanian, S., K. Tus, Q. Z. Li, A. Wang, X. H. Tian, J. Zhou, C. Liang, G. Bartov, L. D. McDaniel, X. J. Zhou, et al. 2006. A Tlr7 translocation accelerates systemic autoimmunity in murine lupus. Proc. Natl. Acad. Sci. USA 103: 9970-9975.
5. Lartigue, A., P. Courville, I. Auquit, A. François, C. Arnoult, F. Tron, D. Gilbert, and P. Musette. 2006. Role of TLR9 in anti-nucleosome and anti-DNA antibody production in lpr mutation-induced murine lupus. J. Immunol. 177: 1349-1354.
6. Nickerson, K. M., S. R. Christensen, J. Shupe, M. Kashgarian, D. Kim, K. Elkon, and M. J. Shlomchik. 2010. TLR9 regulates TLR7-and MyD88-dependent autoantibody production and disease in a murine model of lupus. J. Immunol. 184: 1840-1848.
7. Yu, P., U. Wellmann, S. Kunder, L. Quintanilla-Martinez, L. Jennen, N. Dear, K. Amann, S. Bauer, T. H. Winkler, and H. Wagner. 2006. Toll-like receptor 9-independent aggravation of glomerulonephritis in a novel model of SLE. Int. Immunol. 18: 1211-1219.
8. Santiago-Raber, M. L., I. Dunand-Sauthier, T. Wu, Q. Z. Li, S. Uematsu, S. Akira, W. Reith, C. Mohan, B. L. Kotzin, and S. Izui. 2010. Critical role of TLR7 in the acceleration of systemic lupus erythematosus in TLR9-deficient mice. J. Autoimmun. 34: 339-348.
9. Jackson, S. W., N. E. Scharping, N. S. Kolhatkar, S. Khim, M. A. Schwartz, Q. Z. Li, K. L. Hudkins, C. E. Alpers, D. Liggitt, and D. J. Rawlings. 2014. Opposing impact of B cell-intrinsic TLR7 and TLR9 signals on autoantibody repertoire and systemic inflammation. J. Immunol. 192: 4525-4532.
10. Chan, O. T., L. G. Hannum, A. M. Haberman, M. P. Madaio, and M. J. Shlomchik. 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.
11. Teichmann, L. L., D. Schenten, R. Medzhitov, M. Kashgarian, and M. J. Shlomchik. 2013. Signals via the adaptor MyD88 in B cells and DCs make distinct and synergistic contributions to immune activation and tissue damage in lupus. Immunity 38: 528-540.
12. Shlomchik, M. J., D. Zharhary, T. Saunders, S. A. Camper, and M. G. Weigert. 1993. A rheumatoid factor transgenic mouse model of autoantibody regulation. Int. Immunol. 5: 1329-1341.
13. Sweet, R. A., S. R. Christensen, M. L. Harris, J. Shupe, J. L. Sutherland, and M. J. Shlomchik. 2010. A new site-directed transgenic rheumatoid factor mouse model demonstrates extrafollicular class switch and plasmablast formation. Autoimmunity 43: 607-618.
14. Wolfowicz, C. B., P. Sakorafas, T. L. Rothstein, and A. Marshak-Rothstein. 1988. Oligoclonality of rheumatoid factors arising spontaneously in lpr/lpr mice. Clin. Immunol. Immunopathol. 46: 382-395.
15. Nündel, K., P. Busto, M. Debatis, and A. Marshak-Rothstein. 2013. The role of Bruton's tyrosine kinase in the development and BCR/TLR-dependent activation of AM14 rheumatoid factor B cells. J. Leukoc. Biol. 94: 865-875.
16. Viglianti, G. A., C. M. Lau, T. M. Hanley, B. A. Miko, M. J. Shlomchik, and A. Marshak-Rothstein. 2003. Activation of autoreactive B cells by CpG dsDNA. Immunity 19: 837-847.
17. Lau, C. M., C. Broughton, A. S. Tabor, S. Akira, R. A. Flavell, M. J. Mamula, S. R. Christensen, M. J. Shlomchik, G. A. Viglianti, I. R. Rifkin, and A. Marshak-Rothstein. 2005. RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement. J. Exp. Med. 202: 1171-1177.
18. Uccellini, M. B., L. Busconi, N. M. Green, P. Busto, S. R. Christensen, M. J. Shlomchik, A. Marshak-Rothstein, and G. A. Viglianti. 2008. Autoreactive B cells discriminate CpG-rich and CpG-poor DNA and this response is modulated by IFN-alpha. J. Immunol. 181: 5875-5884.
19. Green, N. M., A. Laws, K. Kiefer, L. Busconi, Y. M. Kim, M. M. Brinkmann, E. H. Trail, K. Yasuda, S. R. Christensen, M. J. Shlomchik, et al. 2009. Murine B cell response to TLR7 ligands depends on an IFN-beta feedback loop. J. Immunol. 183: 1569-1576.
20. Prak, E. L., and M. Weigert. 1995. Light chain replacement: a new model for antibody gene rearrangement. J. Exp. Med. 182: 541-548.
21. Monestier, M., and K. E. Novick. 1996. Specificities and genetic characteristics of nucleosome-reactive antibodies from autoimmune mice. Mol. Immunol. 33: 89-99.
22. Monestier, M., K. E. Novick, and M. J. Losman. 1994. D-penicillamine-and quinidine-induced antinuclear antibodies in A.SW (H-2s) mice: similarities with autoantibodies in spontaneous and heavy metal-induced autoimmunity. Eur. J. Immunol. 24: 723-730.
23. Eilat, D., and R. Fischel. 1991. Recurrent utilization of genetic elements in V regions of antinucleic acid antibodies from autoimmune mice. J. Immunol. 147: 361-368.
24. Lenert, P., K. Yasuda, L. Busconi, P. Nelson, C. Fleenor, R. S. Ratnabalasuriar, P. L. Nagy, R. F. Ashman, I. R. Rifkin, and A. Marshak-Rothstein. 2009. DNAlike class R inhibitory oligonucleotides (INH-ODNs) preferentially block autoantigen-induced B-cell and dendritic cell activation in vitro and autoantibody production in lupus-prone MRL-Fas(lpr/lpr) mice in vivo. Arthritis Res. Ther. 11: R79.
25. Kanno, A., C. Yamamoto, M. Onji, R. Fukui, S. Saitoh, Y. Motoi, T. Shibata, F. Matsumoto, T. Muta, and K. Miyake. 2013. Essential role for Toll-like receptor 7 (TLR7)-unique cysteines in an intramolecular disulfide bond, proteolytic cleavage and RNA sensing. Int. Immunol. 25: 413-422.
26. Herlands, R. A., S. R. Christensen, R. A. Sweet, U. Hershberg, and M. J. Shlomchik. 2008. T cell-independent and toll-like receptor-dependent antigen-driven activation of autoreactive B cells. Immunity 29: 249-260.
27. Calame, K. L., K. I. Lin, and C. Tunyaplin. 2003. Regulatory mechanisms that determine the development and function of plasma cells. Annu. Rev. Immunol. 21: 205-230.
28. Angelin-Duclos, C., G. Cattoretti, K. I. Lin, and K. Calame. 2000. Commitment of B lymphocytes to a plasma cell fate is associated with Blimp-1 expression in vivo. J. Immunol. 165: 5462-5471.
29. Sciammas, R., A. L. Shaffer, J. H. Schatz, H. Zhao, L. M. Staudt, and H. Singh. 2006. Graded expression of interferon regulatory factor-4 coordinates isotype switching with plasma cell differentiation. Immunity 25: 225-236.
30. Shaffer, A. L., K. I. Lin, T. C. Kuo, X. Yu, E. M. Hurt, A. Rosenwald, J. M. Giltnane, L. Yang, H. Zhao, K. Calame, and L. M. Staudt. 2002. Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program. Immunity 17: 51-62.
31. Tarte, K., F. Zhan, J. De Vos, B. Klein, and J. Shaughnessy, Jr. 2003. Gene expression profiling of plasma cells and plasmablasts: toward a better understanding of the late stages of B-cell differentiation. Blood 102: 592-600.
32. Shaffer, A. L., M. Shapiro-Shelef, N. N. Iwakoshi, A. H. Lee, S. B. Qian, H. Zhao, X. Yu, L. Yang, B. K. Tan, A. Rosenwald, et al. 2004. XBP1, downstream of Blimp-1, expands the secretory apparatus and other organelles, and increases protein synthesis in plasma cell differentiation. Immunity 21: 81-93.
33. Ochiai, K., M. Maienschein-Cline, G. Simonetti, J. Chen, R. Rosenthal, R. Brink, A. S. Chong, U. Klein, A. R. Dinner, H. Singh, and R. Sciammas. 2013. Transcriptional regulation of germinal center B and plasma cell fates by dynamical control of IRF4. Immunity 38: 918-929.
34. Feng, J., H. Wang, D. M. Shin, M. Masiuk, C. F. Qi, and H. C. Morse, III. 2011. IFN regulatory factor 8 restricts the size of the marginal zone and follicular B cell pools. J. Immunol. 186: 1458-1466.
35. Fukui, R., S. Saitoh, A. Kanno, M. Onji, T. Shibata, A. Ito, M. Onji, M. Matsumoto, S. Akira, N. Yoshida, and K. Miyake. 2011. Unc93B1 restricts systemic lethal inflammation by orchestrating Toll-like receptor 7 and 9 trafficking. Immunity 35: 69-81.
36. Boulé, M. W., C. Broughton, F. Mackay, S. Akira, A. Marshak-Rothstein, and I. R. Rifkin. 2004. Toll-like receptor 9-dependent and-independent dendritic cell activation by chromatin-immunoglobulin G complexes. J. Exp. Med. 199: 1631-1640.
37. Scapini, P., A. Carletto, B. Nardelli, F. Calzetti, V. Roschke, F. Merigo, N. Tamassia, S. Pieropan, D. Biasi, A. Sbarbati, et al. 2005. Proinflammatory mediators elicit secretion of the intracellular B-lymphocyte stimulator pool (BLyS) that is stored in activated neutrophils: implications for inflammatory diseases. Blood 105: 830-837.
38. Christensen, S. R., M. Kashgarian, L. Alexopoulou, R. A. Flavell, S. Akira, and M. J. Shlomchik. 2005. Toll-like receptor 9 controls anti-DNA autoantibody production in murine lupus. J. Exp. Med. 202: 321-331.
39. Nickerson, K. M., J. L. Cullen, M. Kashgarian, and M. J. Shlomchik. 2013. Exacerbated autoimmunity in the absence of TLR9 in MRL.Fas(lpr) mice depends on Ifnar1. J. Immunol. 190: 3889-3894.
40. Desnues, B., A. B. Macedo, A. Roussel-Queval, J. Bonnardel, S. Henri, O. Demaria, and L. Alexopoulou. 2014. TLR8 on dendritic cells and TLR9 on B cells restrain TLR7-mediated spontaneous autoimmunity in C57BL/6 mice. Proc. Natl. Acad. Sci. USA 111: 1497-1502.
41. Nickerson, K. M., S. R. Christensen, J. L. Cullen, W. Meng, E. T. Luning Prak, and M. J. Shlomchik. 2013. TLR9 promotes tolerance by restricting survival of anergic anti-DNA B cells, yet is also required for their activation. J. Immunol. 190: 1447-1456.
42. Rui, L., J. I. Healy, J. Blasioli, and C. C. Goodnow. 2006. ERK signaling is a molecular switch integrating opposing inputs from B cell receptor and T cell cytokines to control TLR4-driven plasma cell differentiation. J. Immunol. 177: 5337-5346.
43. Rui, L., C. G. Vinuesa, J. Blasioli, and C. C. Goodnow. 2003. Resistance to CpG DNA-induced autoimmunity through tolerogenic B cell antigen receptor ERK signaling. Nat. Immunol. 4: 594-600.
44. Boeglin, E., C. R. Smulski, S. Brun, S. Milosevic, P. Schneider, and S. Fournel. 2011. Toll-like receptor agonists synergize with CD40L to induce either proliferation or plasma cell differentiation of mouse B cells. PLoS ONE 6: e25542.
45. Genestier, L., M. Taillardet, P. Mondiere, H. Gheit, C. Bella, and T. Defrance. 2007. TLR agonists selectively promote terminal plasma cell differentiation of B cell subsets specialized in thymus-independent responses. J. Immunol. 178: 7779-7786.
46. Pathak, S., S. Ma, V. Shukla, and R. Lu. 2013. A role for IRF8 in B cell anergy. J. Immunol. 191: 6222-6230.
47. Stoehr, A. D., C. T. Schoen, M. M. Mertes, S. Eiglmeier, V. Holecska, A. K. Lorenz, T. Schommartz, A. L. Schoen, C. Hess, A. Winkler, et al. 2011. TLR9 in peritoneal B-1b cells is essential for production of protective selfreactive IgM to control Th17 cells and severe autoimmunity. J. Immunol. 187: 2953-2965.
48. Soni, C., E. B. Wong, P. P. Domeier, T. N. Khan, T. Satoh, S. Akira, and Z. S. Rahman. 2014. B cell-intrinsic TLR7 signaling is essential for the development of spontaneous germinal centers. J. Immunol. 193: 4400-4414.
49. Fukui, R., S. Saitoh, F. Matsumoto, H. Kozuka-Hata, M. Oyama, K. Tabeta, B. Beutler, and K. Miyake. 2009. Unc93B1 biases Toll-like receptor responses to nucleic acid in dendritic cells toward DNA-but against RNA-sensing. J. Exp. Med. 206: 1339-1350.