Mice deficient in nuclear factor (NF)-κB/p52 present with defects in humoral responses, germinal center reactions, and splenic microarchitecture

Journal of Experimental Medicine

Volumn 187, Issue 2, 1998, Pages 147-159

  Franzoso, Guido ^a   Carlson, Louise ^a   Poljak, Ljiljana ^a   Shores, Elizabeth W ^c   Epstein, Suzanne ^c   Leonardi, Antonio ^a   Grinberg, Alex ^b   Tran, Tom ^c   Scharton Kersten, Tanya ^a   Anver, Miriam ^d   Love, Paul ^b   Brown, Keith ^a   Siebenlist, Ulrich ^a  

^a NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^b EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT   (United States)

^c CENTER FOR DRUG EVALUATION AND RESEARCH   (United States)

^d SAIC FREDERICK INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

IMMUNOGLOBULIN ENHANCER BINDING PROTEIN;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; B LYMPHOCYTE; CONTROLLED STUDY; CYTOARCHITECTURE; DENDRITIC CELL; GERMINAL CENTER; IMMUNE DEFICIENCY; LYMPH FOLLICLE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEFICIENCY; T LYMPHOCYTE; TRANSCRIPTION REGULATION;

ADOPTIVE TRANSFER; ANIMALS; ANTIBODY FORMATION; B-LYMPHOCYTE SUBSETS; GERMINAL CENTER; IMMUNOLOGIC DEFICIENCY SYNDROMES; LYMPHOCYTE COUNT; MICE; MICE, INBRED STRAINS; MICE, KNOCKOUT; NF-KAPPA B; PROTO-ONCOGENE PROTEINS; SPLEEN; T-LYMPHOCYTE SUBSETS; TOXOPLASMA; TOXOPLASMOSIS, ANIMAL;

EID: 0031964855     PISSN: 00221007     EISSN: None     Source Type: Journal    
DOI: 10.1084/jem.187.2.147     Document Type: Article

References (62)

1. Baeuerle, P.A., and T. Henkel. 1994. Function and activation of NF-κB in the immune system. Annu. Rev. Immunol. 12: 141-179.
2. Siebenlist, U., G. Franzoso, and K. Brown. 1994. Structure, regulation and function of NF-κB. Annu. Rev. Cell Biol. 10: 405-455.
3. Verma, I.M., J.K. Stevenson, E.M. Schwarz, D.V. Antwerp, and S. Miyamoto. 1995. Rel/NF-κB/IκB family: intimate tales of association and dissociation. Genes Dev. 9:2723-2735.
4. Baldwin, A.S. 1996. The NF-κB and IκB proteins: new discoveries and insights. Annu. Rev. Immunol. 14:649-681.
5. Brown, K., S. Gerstberger, L. Carlson, G. Franzoso, and U. Siebenlist. 1995. Control of IκB-α proteolysis by site-specific signal-induced phosphorylation. Science. 267:1485-1488.
6. Chen, Z.J., L. Parent, and T. Maniatis. 1996. Site-specific phosphorylation of IκB-α by a novel ubiquitination-dependent protein kinase activity. Cell. 84:853-862.
7. Naumann, M.F., and C. Scheidereit. 1994. Activation of NF-κB in vivo is regulated by multiple phosphorylations. EMBO (Eur. Mol. Biol. Organ.) J. 13:4597-4607.
8. Zhong, H., H. SuYang, H. Erdjument-Bromage, P. Tempst, and S. Ghosh. 1997. The transcriptional activity of NF-κB is regulated by the IκB-associated PKAc subunit through a cyclic AMP-independent mechanism. Cell. 89:413-424.
9. Ohno, H., G. Takimoto, and T.W. McKeithan. 1990. The candidate proto-oncogene bcl-3 is related to genes implicate in cell lineage determination and cell cycle control. Cell. 60: 991-997.
10. Franzoso, G., V. Bours, S. Park, M. Tomita-Yamaguchi, K. Kelly, and U. Siebenlist. 1992. The candidate oncoprotein Bcl-3 is an antagonist of p50/NF-κB-mediated inhibition. Nature. 359:339-342.
11. Franzoso, G., V. Bours, V. Azarenko, S. Park, M. Tomita-Yamaguchi, T. Kanno, K. Brown, and U. Siebenlist. 1993. The oncoprotein Bcl-3 can facilitate NF-κB-mediated transactivation by removing inhibiting p50 homodimers from select KB sites. EMBO (Eur. Mol. Biol. Organ.) J. 12:3893-3901.
12. Hatada, E.N., N. Nieters, F.G. Wulczyn, M. Naumann, R. Meyer, G. Nucifora, T.W. McKeithan, and C. Scheidereit. 1992. The ankyrin repeat domains of the NF-κB precursor p105 and the proto-oncogene bcl-3 act as specific inhibitors of NF-κB DNA binding. Proc. Natl. Acad. Sci. USA. 89: 2489-2493.
13. Wulczyn, F.G., M. Naumann, and C. Scheidereit. 1992. Candidate proto-oncogene bcl-3 encodes a subunit-specific inhibitor of transcription factor NF-κB. Nature. 358:597-599.
14. Bours, V., G. Franzoso, V. Azarenko, S. Park, T. Kanno, K. Brown, and U. Siebenlist. 1993. The oncoprotein Bcl-3 directly transactivates through κB motifs via association with DNA-binding p50B homodimers. Cell. 72:729-739.
15. Naumann, M., F.G. Wulczyn, and C. Scheidereit. 1993. The NF-κB precursor p105 and the proto-oncogene product Bcl-3 are IκB molecules and control nuclear translocation of NF-κB. EMBO (Eur. Mol. Biol. Organ.) J. 12:213-222.
16. Nolan, G.P., T. Fujita, K. Bhatia, K. Huppi, H.-C. Liou, M.L. Scott, and D. Baltimore. 1993. The bcl-3 proto-oncogene encodes a nuclear IκB-like molecule that preferentially interacts with NF-κB p50 in a phosphorylation-dependent manner. Mol. Cell. Biol. 13:3557-3566.
17. Zhang, Q., J.A. Didonato, M. Karin, and T.W. McKeithan. 1994. BCL3 encodes a nuclear protein which can alter the subcellular localization of NF-κB proteins. Mol. Cell. Biol. 14:3915-3926.
18. Fujita, T., G.P. Nolan, H.-C. Liou, M.L. Scott, and D. Baltimore. 1993. The candidate proto-oncogene bcl-3 encodes a transcriptional coactivator that activates through NF-κB p50 homodimers. Genes Dev. 7:1354-1363.
19. Caamano, J.H., P. Perez, S.A. Lira, and R. Bravo. 1996. Constitutive expression of Bcl-3 in thymocytes increases the DNA binding of NF-κB1 (p50) homodimers in vivo. Mol. Cell. Biol. 16:342-1348.
20. Neri, A., C.C. Chang, L. Lombardi, M. Salina, P. Corradini, A.T. Maiolo, R.S. Chaganti, and R. Dalla-Favera. 1991. B cell lymphoma-associated chromsomal translocation involves candidate oncogene lyt-10 homologous to NF-κB p50. Cell. 67:1075-1087.
21. Neri, A., N.S. Fracchiolla, A. Migliazza, D. Trecca, and L. Lombardi. 1996. The involvement of the candidate protooncogene NF-κB2/lyt-10 in lymphoid malignancies. Leuk. Lymphoma. 23:43-48.
22. Fracchiolla, N.S., L. Lombardi, M. Salina, A. Migliazza, L. Baldini, E. Berti, L. Cro, E. Polli, A.T. Maiolo, and A. Neri. 1993. Structural alterations of the NF-κB transcription factor lyt-10 in lymphoid malignancies. Oncogene. 8:2839-2845.
23. Michaux, L., J. Dierlamm, I. Wlodarska, V. Bours, H.V.D. Berghe, and A. Hagemeijer. 1997. t(14;10)/BCL3 rearrangements in lymphoproliferative disorders: a review of 23 cases. Cancer Genet. Cytogenet. 94:36-43.
24. Sha, W.C., H.C. Liou, E.I. Tuomanen, and D. Baltimore. 1995. Targeted disruption of the p50 subunit of NF-κB leads to multitocal defects in immune responses. Cell. 80:321-330.
25. Beg, A.A., W.C. Sha, R.T. Bronson, and D. Baltimore. 1995. Constitutive NF-κB activation, enhanced granulopoiesis, and neonatal lethality in IκBα-deficient mice. Genes Dev. 9:2736-2746.
26. Klement, J.F., N.R. Rice, B.D. Car, S.J. Abbondanzo, G.D. Powers, P.H. Bhatt, C.H. Chen, C.A. Rosen, and C.L. Stewart. 1996. IκBα deficiency results in sustained NF-κB response and severe widespread dermatitis in mice. Mol. Cell. Biol. 16:2341-2349.
27. Kontgen, F., R.J. Grumont, A. Strasser, D. Metcalf, R. Li, D. Tarlinton, and S. Gerondakis. 1995. Mice lacking the c-rel proto-oncogene exhibit defects in lymphocyte proliferation, humoral immunity, and interleukin-2 expression. Genes Dev. 9:1965-1977.
28. Burkly, L., C. Hession, L. Ogata, C. Reilly, L.A. Marconi, D. Olson, R. Tizard, R. Cate, and D. Lo. 1995. Expression of relB is required for the development of thymic medulla and dendritic cells. Nature. 373:531-536.
29. Weih, F., D. Carrasco, S.K. Durham, D.S. Barton, C.A. Rizzo, R.P. Ryseck, S.A. Lira, and R. Bravo. 1995. Multiorgan inflammation and hematopoietic abnormalities in mice with a targeted disruption of RelB, a member of the NF-κB/ Rel family. Cell. 80:331-340.
30. Beg, A.A., W.C. Sha, R.T. Bronson, S. Ghosh, and D. Baltimore. 1995. Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-κB. Nature. 376:167-170.
31. Doi, T.S., T. Takahashi, O. Taguchi, T. Azuma, and Y. Obata. 1997. NF-κB RelA-deficient lymphocytes: normal development of T cells and B cells, impaired production of IgA and IgG1 and reduced proliferative responses. J. Exp. Med. 185:953-961.
32. Franzoso, G., L. Carlson, T. Sharton-Kersten, E.W. Shores, S. Epstein, A. Grinberg, T. Tran, E. Shacter, A. Leonardi, M. Anver, et al. 1997. Critical roles for the Bcl-3 oncoprotein in T cell-mediated immunity, splenic microarchitecture and germinal center reactions. Immunity. 6:479-490.
33. Schwarz, E.M., P. Krimpenfort, A. Berns, and I.M. Verma. 1997. Immunological detects in mice with a targeted disruption in Bcl-3. Genes Dev. 11:187-197.
34. Tybulewicz, V.L.J., C.E. Crawford, P.K. Jackson, R.T. Bronson, and R.C. Mulligan. 1991. Neonatal lethality and lymphoenia in mice with homozygous disruption of the c-abl proto-oncogene. Cell. 2:223-238.
35. Cao, X., E.W. Shores, J. Hu-Li, M.R. Anver, B.L. Kelsall, S.M. Russell, J. Drago, M. Noguchi, A. Grinberg, E.T. Bloom, et al. 1995. Defective lymphoid development in mice lacking expression of the common cytokine receptor γ chain. Immunity. 2:223-238.
36. Dignam, J.D., R.M. Lebovitz, and R.C. Roeder. 1983. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 11:1475-1489.
37. Ghosh, S., A.M. Gifford, L.R. Riviere, P. Tempst, G.P. Nolan, and D. Baltimore. 1990. Cloning of the p50 DNA binding subunit of NF-κB: homology to rel and dorsal. Cell. 62: 1019-1029.
38. Bours, V., P.R. Burd, K. Brown, J. Villalobos, S. Park, R. Ryseck, R. Bravo, K. Kelly, and U. Siebenlist. 1992. A novel mitogen-inducible gene product related to p50-p105-NF-κB participates in transactivation through a κB site. Mol. Cell. Biol. 12:685-695.
39. Franzoso, G., P. Biswas, G. Poli, L.M. Carlson, K.D. Brown, M. Tomita-Yamaguchi, A.S. Fauci, and U. Siebenlist. 1994. A family of serine proteases expressed exclusively in myelomonocytic cells specifically processes the nuclear factor-κB subunit p65 in vitro and may impair human immunodeficiency virus replication in these cells. J. Exp. Med. 180:1445-1456.
40. Shores, E.W., K. Huang, T. Tran, E. Lee, A. Grinberg, and P.E. Love. 1994. Role of TCR ζ chain in T cell development and selection. Science. 266:1047-1050.
41. Stüber, E., and W. Strober. 1996. Distinct populations of dendritic cells are present in the subepithelial dome and T cell regions of the murine Peyer's patch. J. Exp. Med. 183:979-989.
42. Kelsall, B.L., and W. Strober. 1996. Distinct populations of dendritic cells are present in the subepithelial dome and T cell regions of the murine Peyer's patch. J. Exp. Med. 165:64-69.
43. Coutelier, J.P., J.T. van der Logt, F.W. Heessen, G. Warnier, and J. Van Snick. 1987. IgG2a restriction of murine antibodies elicited by viral infections. J. Exp. Med. 165:64-69.
44. Borriello, F., M.P. Sethna, S.D. Boyd, A.N. Schweitzer, E.A. Tivol, D. Jacoby, T.B. Strom, E.M. Simpson, G.J. Freeman, and A.M. Sharpe. 1997. B7-1 and B7-2 have overlapping, critical roles in immunoglobulin class switching and germinal center formation. Immunity. 6:303-313.
45. Mombaerts, P., J. Iacommi, R.S. Johnson, K. Herrup, S. Tonegawa, and V.E. Papaioannou. 1992. RAG-1-deficient mice have no mature B and T lymphocytes. Cell. 68:869-877.
46. Leenen, P.J., M.F. DeBruijin, J.S. Voerman, P.A. Campbell, and W. van Ewijk. 1994. Markers of mouse macrophage development detected by monoclonal antibodies. J. Immunol. Methods. 174:5-19.
47. Liu, Y.-J., and J. Banchereau. 1996. Mutant mice without B lymphocyte follicles. J. Exp. Med. 184:1207-1211.
48. Koni, P.A., R. Sacca, P. Lawton, J.L. Browning, N.H. Ruddle, and R.A. Flavell. 1997. Distinct roles in lymphoid organogenesis for lymphotoxins α and β revealed in lymphotoxin β-deficient mice. Immunity. 6:491-500.
49. Feuillard, J.M., M. Koerner, A. Israel, J. Vassy, and M. Raphael. 1996. Differential nuclear localization of p50, p42, and relB proteins in human accessory cells of the immune response in situ. Eur. J. Immunol. 26:2547-2551.
50. Fu, Y.X., H. Molina, M. Matsumoto, G. Huang, J. Min, and D.D. Chaplin. 1997. Lymphotoxin-α (LTα) supports development of splenic follicular structure that is required for IgG responses. J. Exp. Med. 185:2111-2120.
51. Matsumoto, M., S.F. Lo, C.J. Carruthers, J. Min, S. Mariathasan, G. Huang, D.R. Plas, S.M. Martin, R.S. Geha, M.H. Nahm, and D.D. Chaplin. 1996. Affinity maturation without germinal centres in lymphotoxin-α deficient mice. Nature. 382:462-466.
52. Pasparakis, M.L., V. Alexopoulou, V. Episkopou, and G. Killias. 1996. Immune and inflammatory responses in TNF-α-deficient mice: a critical requirement for TNF-α in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response. J. Exp. Med. 184:1397-1411.
53. DeTogni, P., J. Goellner, N.H. Ruddle, P.R. Streeter, A. Fick, S. Mariathasan, S.C. Smith, R. Carlson, L.P. Shornick, and J. Schoenberger. 1994. Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science. 264:703-707.
54. LeHir, M., H. Bluethmann, M.H. Kosco-Vilbois, M. Muller, F. di Padova, M. Moore, B. Ryffel, and H.P. Eugster. 1996. Differentiation of follicular dendritic cells and full antibody responses require tumor necrosis factor receptor-1 signaling. J. Exp. Med. 183:2367-2372.
55. Matsumoto, M., S. Manathasan, M.H. Nahm, F. Baranyay, J.J. Peschon, and D.D. Chaplin. 1996. Role of lymphotoxin and the type 1 TNF receptor in the formation of germinal centers. Science. 271:1289-1291.
56. Ettinger, R., J. Browning, S.A. Michie, W. VanEwijk, and H.O. McDevitt. 1996. Disrupted splenic architecture, but normal lymph node development in mice expressing a soluble lymphotoxin-β receptor-IgG1 fusion protein. Proc. Natl. Acad. Sci. USA. 93:13102-13107.
57. Kawabe, T., T. Naka, K. Yoshida, T. Tanaka, H. Fujiwara, S. Suematsu, N. Yoshida, T. Kishimoto, and H. Kikutani. 1994. The immune response in CD40-deficient mice: impaired immunoglobulin class switching and germinal center formation. Immunity. 1:167-178.
58. Xu, J., T.M. Foy, J.D. Laman, E.A. Elliott, J.J. Dunn, T.J. Waldschmidt, J. Elsemore, R.J. Noelle, and R.A. Flavell. 1994. Mice deficient for the CD40 ligand. Immunity. 1:423-431.
59. Grewal, I.S., J. Xu, and R.A. Flavell. 1995. Impairment of antigen-specific T-cell priming in mice lacking CD40 ligand. Nature. 378:617-620.
60. Tewari, M., and V.M. Dixit. 1996. Recent advances in tumor necrosis factor and CD40 signalling. Curr. Opin. Genet. Dev. 6:39-44.
61. Ware, C.F., S. VanArsdale, and T.L. VanArsdale. 1996. Apoptosis mediated by the TNF-related cytokine and receptor families. J. Cell. Biochem. 60:47-55.
62. Scharton-Kersten, T.M., T.A. Wynn, E.Y. Denkers, S. Bala, L. Showe, E. Grunvald, S. Hieny, R.T. Gazzinelli, and A. Sher. 1996. In the absence of endogenous IFN-γ mice develop unimpaired IL-12 response to Toxoplasma gondii while failing to control acute infection. J. Immunol. 157:4045-4054.