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J Exp Med. Oct 1, 1996; 184(4): 1537–1541.
PMCID: PMC2192806

B cells lacking RelB are defective in proliferative responses, but undergo normal B cell maturation to Ig secretion and Ig class switching

Abstract

A number of distinct functional abnormalities have been observed in B cells derived from p50/ NF-kappa B or c-rel knockout mice. RelB, another member of the NF-kappa B/Rel family of transcription factors, is expressed during the latter stages of B cell maturation and can bind to regulatory sites within the Ig heavy chain locus. Therefore, we tested the ability of B cells from relB knockout mice (relB-/-) to proliferate, undergo maturation to IgM secretion, and switch to the expression of downstream Ig isotypes in response to distinct activators including LPS, anti-CD40 mAb or CD40 ligand, and/or dextran anti-IgD antibodies in combination with various cytokines, including IL-4, IL-5, IFN-gamma, and TGF-beta. B cells lacking RelB showed up to 4-fold reductions in DNA synthesis in response to LPS, CD40, and membrane Ig- dependent activation relative to controls. However, relB-/- B cells were comparable to control B cells in their ability to undergo maturation to IgM secretion and switch to the expression of IgG3, IgG1, IgG2b, IgG2a, IgE, and/or IgA under all activation conditions tested. Thus, RelB, like c-Rel and p50/NF-kappa B, plays a role in B cell proliferation. However, in contrast to c-Rel and p50/ NF-kappa B, it is not critically involved in maturation to Ig secretion or expression of Ig isotypes.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Kopp EB, Ghosh S. NF-kappa B and rel proteins in innate immunity. Adv Immunol. 1995;58:1–27. [PubMed]
  • Grilli M, Chiu JJ, Lenardo MJ. NF-kappa B and Rel: participants in a multiform transcriptional regulatory system. Int Rev Cytol. 1993;143:1–62. [PubMed]
  • Baeuerle PA, Henkel T. Function and activation of NF-kappa B in the immune system. Annu Rev Immunol. 1994;12:141–179. [PubMed]
  • Verma IM, Stevenson JK, Schwarz EM, Van Antwerp D, Miyamoto S. Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation. Genes Dev. 1995 Nov 15;9(22):2723–2735. [PubMed]
  • Finco TS, Baldwin AS. Mechanistic aspects of NF-kappa B regulation: the emerging role of phosphorylation and proteolysis. Immunity. 1995 Sep;3(3):263–272. [PubMed]
  • Rooney JW, Dubois PM, Sibley CH. Cross-linking of surface IgM activates NF-kappa B in B lymphocyte. Eur J Immunol. 1991 Dec;21(12):2993–2998. [PubMed]
  • Lalmanach-Girard AC, Chiles TC, Parker DC, Rothstein TL. T cell-dependent induction of NF-kappa B in B cells. J Exp Med. 1993 Apr 1;177(4):1215–1219. [PMC free article] [PubMed]
  • Berberich I, Shu GL, Clark EA. Cross-linking CD40 on B cells rapidly activates nuclear factor-kappa B. J Immunol. 1994 Nov 15;153(10):4357–4366. [PubMed]
  • Liou HC, Sha WC, Scott ML, Baltimore D. Sequential induction of NF-kappa B/Rel family proteins during B-cell terminal differentiation. Mol Cell Biol. 1994 Aug;14(8):5349–5359. [PMC free article] [PubMed]
  • Gerondakis S, Gaff C, Goodman DJ, Grumont RJ. Structure and expression of mouse germline immunoglobulin gamma 3 heavy chain transcripts induced by the mitogen lipopolysaccharide. Immunogenetics. 1991;34(6):392–400. [PubMed]
  • Delphin S, Stavnezer J. Characterization of an interleukin 4 (IL-4) responsive region in the immunoglobulin heavy chain germline epsilon promoter: regulation by NF-IL-4, a C/EBP family member and NF-kappa B/p50. J Exp Med. 1995 Jan 1;181(1):181–192. [PMC free article] [PubMed]
  • Kenter AL, Wuerffel R, Sen R, Jamieson CE, Merkulov GV. Switch recombination breakpoints occur at nonrandom positions in the S gamma tandem repeat. J Immunol. 1993 Nov 1;151(9):4718–4731. [PubMed]
  • Wuerffel R, Jamieson CE, Morgan L, Merkulov GV, Sen R, Kenter AL. Switch recombination breakpoints are strictly correlated with DNA recognition motifs for immunoglobulin S gamma 3 DNA-binding proteins. J Exp Med. 1992 Aug 1;176(2):339–349. [PMC free article] [PubMed]
  • Wuerffel RA, Nathan AT, Kenter AL. Detection of an immunoglobulin switch region-specific DNA-binding protein in mitogen-stimulated mouse splenic B cells. Mol Cell Biol. 1990 Apr;10(4):1714–1718. [PMC free article] [PubMed]
  • Michaelson JS, Singh M, Snapper CM, Sha WC, Baltimore D, Birshtein BK. Regulation of 3' IgH enhancers by a common set of factors, including kappa B-binding proteins. J Immunol. 1996 Apr 15;156(8):2828–2839. [PubMed]
  • Köntgen F, Grumont RJ, Strasser A, Metcalf D, Li R, Tarlinton D, Gerondakis S. Mice lacking the c-rel proto-oncogene exhibit defects in lymphocyte proliferation, humoral immunity, and interleukin-2 expression. Genes Dev. 1995 Aug 15;9(16):1965–1977. [PubMed]
  • Sha WC, Liou HC, Tuomanen EI, Baltimore D. Targeted disruption of the p50 subunit of NF-kappa B leads to multifocal defects in immune responses. Cell. 1995 Jan 27;80(2):321–330. [PubMed]
  • Snapper CM, Zelazowski P, Rosas FR, Kehry MR, Tian M, Baltimore D, Sha WC. B cells from p50/NF-kappa B knockout mice have selective defects in proliferation, differentiation, germ-line CH transcription, and Ig class switching. J Immunol. 1996 Jan 1;156(1):183–191. [PubMed]
  • Weih F, Carrasco D, Durham SK, Barton DS, Rizzo CA, Ryseck RP, Lira SA, Bravo R. Multiorgan inflammation and hematopoietic abnormalities in mice with a targeted disruption of RelB, a member of the NF-kappa B/Rel family. Cell. 1995 Jan 27;80(2):331–340. [PubMed]
  • Burkly L, Hession C, Ogata L, Reilly C, Marconi LA, Olson D, Tizard R, Cate R, Lo D. Expression of relB is required for the development of thymic medulla and dendritic cells. Nature. 1995 Feb 9;373(6514):531–536. [PubMed]
  • Weih F, Ryseck RP, Chen L, Bravo R. Apoptosis of nur77/N10-transgenic thymocytes involves the Fas/Fas ligand pathway. Proc Natl Acad Sci U S A. 1996 May 28;93(11):5533–5538. [PMC free article] [PubMed]
  • Brunswick M, Finkelman FD, Highet PF, Inman JK, Dintzis HM, Mond JJ. Picogram quantities of anti-Ig antibodies coupled to dextran induce B cell proliferation. J Immunol. 1988 May 15;140(10):3364–3372. [PubMed]
  • Kehry MR, Castle BE. Regulation of CD40 ligand expression and use of recombinant CD40 ligand for studying B cell growth and differentiation. Semin Immunol. 1994 Oct;6(5):287–294. [PubMed]
  • Hasbold J, Johnson-Léger C, Atkins CJ, Clark EA, Klaus GG. Properties of mouse CD40: cellular distribution of CD40 and B cell activation by monoclonal anti-mouse CD40 antibodies. Eur J Immunol. 1994 Aug;24(8):1835–1842. [PubMed]
  • Snapper CM, Mond JJ. Towards a comprehensive view of immunoglobulin class switching. Immunol Today. 1993 Jan;14(1):15–17. [PubMed]
  • Buratowski S. The basics of basal transcription by RNA polymerase II. Cell. 1994 Apr 8;77(1):1–3. [PubMed]
  • Arulampalam V, Grant PA, Samuelsson A, Lendahl U, Pettersson S. Lipopolysaccharide-dependent transactivation of the temporally regulated immunoglobulin heavy chain 3' enhancer. Eur J Immunol. 1994 Jul;24(7):1671–1677. [PubMed]
  • McIntyre TM, Kehry MR, Snapper CM. Novel in vitro model for high-rate IgA class switching. J Immunol. 1995 Apr 1;154(7):3156–3161. [PubMed]

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