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J Exp Med. 1991 January 1; 173(1): 1–5.
PMCID: PMC2118767

Activated B lymphocytes from human immunodeficiency virus-infected individuals induce virus expression in infected T cells and a promonocytic cell line, U1

Abstract

Freshly isolated B lymphocytes from patients infected with human immunodeficiency virus (HIV), in contrast to B cells from normal controls, were shown to induce viral expression in two cell lines: ACH- 2, a T cell line, and U1, a promonocytic cell line, which are chronically infected with HIV, as well as in autologous T cells. In 10 out of 10 HIV-infected individuals with hypergammaglobulinemia, spontaneous HIV-inductive capacity was found with highly purified peripheral blood B cells, whereas peripheral blood or tonsillar B cells from six healthy, HIV-negative donors did not induce HIV expression unless the cells were stimulated in vitro. The induction of HIV expression was observed in direct coculture experiments of B lymphocytes and HIV-infected cells, and could also be mediated by supernatants from cultures of B cells. Significantly higher amounts of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) were detected in the B cell culture supernatants from HIV-infected patients with hypergammaglobulinemia (IL-6: mean = 536 pg/ml; TNF-alpha: mean = 493 pg/ml), as compared with normal uninfected controls (IL-6: mean = 18 pg/ml; TNF-alpha: mean = 23 pg/ml). Antibodies against these cytokines abolished the HIV-inductive capacity of B cells. We conclude that in vivo activated B cells in HIV-infected individuals can upregulate the expression of virus in infected cells by secreting cytokines such as TNF-alpha and IL-6, and, therefore, may play a role in the progression of HIV infection.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Rosenberg ZF, Fauci AS. Immunopathogenic mechanisms of HIV infection: cytokine induction of HIV expression. Immunol Today. 1990 May;11(5):176–180. [PubMed]
  • Folks TM, Justement J, Kinter A, Dinarello CA, Fauci AS. Cytokine-induced expression of HIV-1 in a chronically infected promonocyte cell line. Science. 1987 Nov 6;238(4828):800–802. [PubMed]
  • Clouse KA, Powell D, Washington I, Poli G, Strebel K, Farrar W, Barstad P, Kovacs J, Fauci AS, Folks TM. Monokine regulation of human immunodeficiency virus-1 expression in a chronically infected human T cell clone. J Immunol. 1989 Jan 15;142(2):431–438. [PubMed]
  • Poli G, Kinter A, Justement JS, Kehrl JH, Bressler P, Stanley S, Fauci AS. Tumor necrosis factor alpha functions in an autocrine manner in the induction of human immunodeficiency virus expression. Proc Natl Acad Sci U S A. 1990 Jan;87(2):782–785. [PubMed]
  • Poli G, Bressler P, Kinter A, Duh E, Timmer WC, Rabson A, Justement JS, Stanley S, Fauci AS. Interleukin 6 induces human immunodeficiency virus expression in infected monocytic cells alone and in synergy with tumor necrosis factor alpha by transcriptional and post-transcriptional mechanisms. J Exp Med. 1990 Jul 1;172(1):151–158. [PMC free article] [PubMed]
  • Matsuyama T, Hamamoto Y, Soma G, Mizuno D, Yamamoto N, Kobayashi N. Cytocidal effect of tumor necrosis factor on cells chronically infected with human immunodeficiency virus (HIV): enhancement of HIV replication. J Virol. 1989 Jun;63(6):2504–2509. [PMC free article] [PubMed]
  • Lane HC, Masur H, Edgar LC, Whalen G, Rook AH, Fauci AS. Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1983 Aug 25;309(8):453–458. [PubMed]
  • Amadori A, Zamarchi R, Ciminale V, Del Mistro A, Siervo S, Alberti A, Colombatti M, Chieco-Bianchi L. HIV-1-specific B cell activation. A major constituent of spontaneous B cell activation during HIV-1 infection. J Immunol. 1989 Oct 1;143(7):2146–2152. [PubMed]
  • Sung SS, Jung LK, Walters JA, Chen W, Wang CY, Fu SM. Production of tumor necrosis factor/cachectin by human B cell lines and tonsillar B cells. J Exp Med. 1988 Nov 1;168(5):1539–1551. [PMC free article] [PubMed]
  • Muraguchi A, Hirano T, Tang B, Matsuda T, Horii Y, Nakajima K, Kishimoto T. The essential role of B cell stimulatory factor 2 (BSF-2/IL-6) for the terminal differentiation of B cells. J Exp Med. 1988 Feb 1;167(2):332–344. [PMC free article] [PubMed]
  • Yoshizaki K, Matsuda T, Nishimoto N, Kuritani T, Taeho L, Aozasa K, Nakahata T, Kawai H, Tagoh H, Komori T, et al. Pathogenic significance of interleukin-6 (IL-6/BSF-2) in Castleman's disease. Blood. 1989 Sep;74(4):1360–1367. [PubMed]
  • Falkoff RJ, Muraguchi A, Hong JX, Butler JL, Dinarello CA, Fauci AS. The effects of interleukin 1 on human B cell activation and proliferation. J Immunol. 1983 Aug;131(2):801–805. [PubMed]
  • Willey RL, Smith DH, Lasky LA, Theodore TS, Earl PL, Moss B, Capon DJ, Martin MA. In vitro mutagenesis identifies a region within the envelope gene of the human immunodeficiency virus that is critical for infectivity. J Virol. 1988 Jan;62(1):139–147. [PMC free article] [PubMed]
  • Clouse KA, Robbins PB, Fernie B, Ostrove JM, Fauci AS. Viral antigen stimulation of the production of human monokines capable of regulating HIV1 expression. J Immunol. 1989 Jul 15;143(2):470–475. [PubMed]
  • Breen EC, Rezai AR, Nakajima K, Beall GN, Mitsuyasu RT, Hirano T, Kishimoto T, Martinez-Maza O. Infection with HIV is associated with elevated IL-6 levels and production. J Immunol. 1990 Jan 15;144(2):480–484. [PubMed]
  • Yarchoan R, Redfield RR, Broder S. Mechanisms of B cell activation in patients with acquired immunodeficiency syndrome and related disorders. Contribution of antibody-producing B cells, of Epstein-Barr virus-infected B cells, and of immunoglobulin production induced by human T cell lymphotropic virus, type III/lymphadenopathy-associated virus. J Clin Invest. 1986 Aug;78(2):439–447. [PMC free article] [PubMed]
  • Nair MP, Pottathil R, Heimer EP, Schwartz SA. Immunoregulatory activities of human immunodeficiency virus (HIV) proteins: effect of HIV recombinant and synthetic peptides on immunoglobulin synthesis and proliferative responses by normal lymphocytes. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6498–6502. [PubMed]
  • Kehrl JH, Miller A, Fauci AS. Effect of tumor necrosis factor alpha on mitogen-activated human B cells. J Exp Med. 1987 Sep 1;166(3):786–791. [PMC free article] [PubMed]
  • Cerny A, Hügin AW, Hardy RR, Hayakawa K, Zinkernagel RM, Makino M, Morse HC., 3rd B cells are required for induction of T cell abnormalities in a murine retrovirus-induced immunodeficiency syndrome. J Exp Med. 1990 Jan 1;171(1):315–320. [PMC free article] [PubMed]

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