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. 1986 Dec;83(23):9124–9128. doi: 10.1073/pnas.83.23.9124

Stimulatory and inhibitory influences of human immunodeficiency virus on normal B lymphocytes.

S Pahwa, R Pahwa, R A Good, R C Gallo, C Saxinger
PMCID: PMC387087  PMID: 3024167

Abstract

B-lymphocyte dysfunction is a characteristic feature of the acquired immunodeficiency syndrome (AIDS) and of the AIDS-related complex. The aim of the present study was to further examine the influences exercised by the human immunodeficiency virus (HIV; formerly called human T-lymphotropic virus type III or lymphadenopathy-associated virus, HTLV-III/LAV) on normal human B lymphocytes. An unfractionated protein preparation, made from HIV purified by density gradient centrifugation, was previously shown to induce differentiation of normal human B lymphocytes into immunoglobulin-secreting cells. In the present analyses, this B-lymphocyte response peaked on day 6 or 7 after culture initiation and was found to be independent of the requirement for monocytes but to require T cells. Responses could also be elicited in cultures of purified B cells by the addition of T cells that had been exposed to HIV antigen. Inhibitors of protein synthesis (puromycin and cycloheximide) abrogated the responses. In contrast to its stimulatory effects, the same virus preparation was previously shown to inhibit polyclonal responses that are normally elicited in peripheral blood lymphocyte cultures by a T-dependent stimulus (pokeweed mitogen) and T-independent stimulus (Epstein-Barr virus). The present studies suggest that the inhibitory effects of the HIV antigen studied herein are targeted primarily at the B lymphocytes. The role of T lymphocytes in the HIV antigen-mediated inhibitory effects, although demonstrated, could not be conclusively established as an essential pathway. These findings elucidate mechanisms by which components of HIV exert stimulatory as well as inhibitory effects on human B lymphocytes and thereby lead to the dysfunction of these cells in HIV infection.

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Selected References

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  1. Allan J. S., Coligan J. E., Barin F., McLane M. F., Sodroski J. G., Rosen C. A., Haseltine W. A., Lee T. H., Essex M. Major glycoprotein antigens that induce antibodies in AIDS patients are encoded by HTLV-III. Science. 1985 May 31;228(4703):1091–1094. doi: 10.1126/science.2986290. [DOI] [PubMed] [Google Scholar]
  2. Barré-Sinoussi F., Chermann J. C., Rey F., Nugeyre M. T., Chamaret S., Gruest J., Dauguet C., Axler-Blin C., Vézinet-Brun F., Rouzioux C. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):868–871. doi: 10.1126/science.6189183. [DOI] [PubMed] [Google Scholar]
  3. Berlinger N. T., Lopez C., Good R. A. Facilitation or attenuation of mixed leukocyte culture responsiveness by adherent cells. Nature. 1976 Mar 11;260(5547):145–146. doi: 10.1038/260145a0. [DOI] [PubMed] [Google Scholar]
  4. Broder S., Gallo R. C. A pathogenic retrovirus (HTLV-III) linked to AIDS. N Engl J Med. 1984 Nov 15;311(20):1292–1297. doi: 10.1056/NEJM198411153112006. [DOI] [PubMed] [Google Scholar]
  5. Casareale D., Sinangil F., Hedeskog M., Ward W., Volsky D. J., Sonnabend J. Establishment of retrovirus-, Epstein-Barr virus-positive B-lymphoblastoid cell lines derived from individuals at risk for acquired immune deficiency syndrome (AIDS). AIDS Res. 1983 1984;1(4):253–270. doi: 10.1089/aid.1.1983.1.253. [DOI] [PubMed] [Google Scholar]
  6. Cianciolo G. J., Copeland T. D., Oroszlan S., Snyderman R. Inhibition of lymphocyte proliferation by a synthetic peptide homologous to retroviral envelope proteins. Science. 1985 Oct 25;230(4724):453–455. doi: 10.1126/science.2996136. [DOI] [PubMed] [Google Scholar]
  7. Dalgleish A. G., Beverley P. C., Clapham P. R., Crawford D. H., Greaves M. F., Weiss R. A. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984 Dec 20;312(5996):763–767. doi: 10.1038/312763a0. [DOI] [PubMed] [Google Scholar]
  8. Denner J., Wunderlich V., Sydow G. Suppression of human lymphocyte mitogen response by retroviruses of type D. I. Action of highly purified intact and disrupted virus. Arch Virol. 1985;86(3-4):177–186. doi: 10.1007/BF01309823. [DOI] [PubMed] [Google Scholar]
  9. Fauci A. S. Immunologic abnormalities in the acquired immunodeficiency syndrome (AIDS). Clin Res. 1984 Dec;32(5):491–499. [PubMed] [Google Scholar]
  10. Fauci A. S., Lane H. C., Volkman D. J. Activation and regulation of human immune responses: implications in normal and disease states. Ann Intern Med. 1983 Jul;99(1):61–75. doi: 10.7326/0003-4819-99-1-61. [DOI] [PubMed] [Google Scholar]
  11. Fauci A. S., Macher A. M., Longo D. L., Lane H. C., Rook A. H., Masur H., Gelmann E. P. NIH conference. Acquired immunodeficiency syndrome: epidemiologic, clinical, immunologic, and therapeutic considerations. Ann Intern Med. 1984 Jan;100(1):92–106. doi: 10.7326/0003-4819-100-1-92. [DOI] [PubMed] [Google Scholar]
  12. Finelt M., Hoffmann M. K. A human monocyte function test: release of B-cell differentiation factor (BDF). Clin Immunol Immunopathol. 1979 Mar;12(3):281–288. doi: 10.1016/0090-1229(79)90031-x. [DOI] [PubMed] [Google Scholar]
  13. Gallo R. C., Salahuddin S. Z., Popovic M., Shearer G. M., Kaplan M., Haynes B. F., Palker T. J., Redfield R., Oleske J., Safai B. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science. 1984 May 4;224(4648):500–503. doi: 10.1126/science.6200936. [DOI] [PubMed] [Google Scholar]
  14. Gronowicz E., Coutinho A., Melchers F. A plaque assay for all cells secreting Ig of a given type or class. Eur J Immunol. 1976 Aug;6(8):588–590. doi: 10.1002/eji.1830060812. [DOI] [PubMed] [Google Scholar]
  15. Ho D. D., Rota T. R., Schooley R. T., Kaplan J. C., Allan J. D., Groopman J. E., Resnick L., Felsenstein D., Andrews C. A., Hirsch M. S. Isolation of HTLV-III from cerebrospinal fluid and neural tissues of patients with neurologic syndromes related to the acquired immunodeficiency syndrome. N Engl J Med. 1985 Dec 12;313(24):1493–1497. doi: 10.1056/NEJM198512123132401. [DOI] [PubMed] [Google Scholar]
  16. Hoffmann M. K. Antigen-specific induction and regulation of antibody synthesis in cultures of human peripheral blood mononuclear cells. Proc Natl Acad Sci U S A. 1980 Feb;77(2):1139–1143. doi: 10.1073/pnas.77.2.1139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. JERNE N. K., NORDIN A. A. Plaque formation in agar by single antibody-producing cells. Science. 1963 Apr 26;140(3565):405–405. [PubMed] [Google Scholar]
  18. KAPLOW L. S. SIMPLIFIED MYELOPEROXIDASE STAIN USING BENZIDINE DIHYDROCHLORIDE. Blood. 1965 Aug;26:215–219. [PubMed] [Google Scholar]
  19. Kalish R. S., Schlossman S. F. The T4 lymphocyte in AIDS. N Engl J Med. 1985 Jul 11;313(2):112–113. doi: 10.1056/NEJM198507113130210. [DOI] [PubMed] [Google Scholar]
  20. Klatzmann D., Champagne E., Chamaret S., Gruest J., Guetard D., Hercend T., Gluckman J. C., Montagnier L. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature. 1984 Dec 20;312(5996):767–768. doi: 10.1038/312767a0. [DOI] [PubMed] [Google Scholar]
  21. Lane H. C., Depper J. M., Greene W. C., Whalen G., Waldmann T. A., Fauci A. S. Qualitative analysis of immune function in patients with the acquired immunodeficiency syndrome. Evidence for a selective defect in soluble antigen recognition. N Engl J Med. 1985 Jul 11;313(2):79–84. doi: 10.1056/NEJM198507113130204. [DOI] [PubMed] [Google Scholar]
  22. Lane H. C., Masur H., Edgar L. C., Whalen G., Rook A. H., Fauci A. S. 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. doi: 10.1056/NEJM198308253090803. [DOI] [PubMed] [Google Scholar]
  23. Mathes L. E., Olsen R. G., Hebebrand L. C., Hoover E. A., Schaller J. P., Adams P. W., Nichols W. S. Immunosuppressive properties of a virion polypeptide, a 15,000-dalton protein, from feline leukemia virus. Cancer Res. 1979 Mar;39(3):950–955. [PubMed] [Google Scholar]
  24. Montagnier L., Gruest J., Chamaret S., Dauguet C., Axler C., Guétard D., Nugeyre M. T., Barré-Sinoussi F., Chermann J. C., Brunet J. B. Adaptation of lymphadenopathy associated virus (LAV) to replication in EBV-transformed B lymphoblastoid cell lines. Science. 1984 Jul 6;225(4657):63–66. doi: 10.1126/science.6328661. [DOI] [PubMed] [Google Scholar]
  25. Pahwa S. G., Quilop M. T., Lange M., Pahwa R. N., Grieco M. H. Defective B-lymphocyte function in homosexual men in relation to the acquired immunodeficiency syndrome. Ann Intern Med. 1984 Dec;101(6):757–763. doi: 10.7326/0003-4819-101-6-757. [DOI] [PubMed] [Google Scholar]
  26. Pahwa S., Pahwa R., Saxinger C., Gallo R. C., Good R. A. Influence of the human T-lymphotropic virus/lymphadenopathy-associated virus on functions of human lymphocytes: evidence for immunosuppressive effects and polyclonal B-cell activation by banded viral preparations. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8198–8202. doi: 10.1073/pnas.82.23.8198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Popovic M., Flomenberg N., Volkman D. J., Mann D., Fauci A. S., Dupont B., Gallo R. C. Alteration of T-cell functions by infection with HTLV-I or HTLV-II. Science. 1984 Oct 26;226(4673):459–462. doi: 10.1126/science.6093248. [DOI] [PubMed] [Google Scholar]
  28. Popovic M., Read-Connole E., Gallo R. C. T4 positive human neoplastic cell lines susceptible to and permissive for HTLV-III. Lancet. 1984 Dec 22;2(8417-8418):1472–1473. doi: 10.1016/s0140-6736(84)91666-0. [DOI] [PubMed] [Google Scholar]
  29. Popovic M., Sarngadharan M. G., Read E., Gallo R. C. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science. 1984 May 4;224(4648):497–500. doi: 10.1126/science.6200935. [DOI] [PubMed] [Google Scholar]
  30. Resnick L., diMarzo-Veronese F., Schüpbach J., Tourtellotte W. W., Ho D. D., Müller F., Shapshak P., Vogt M., Groopman J. E., Markham P. D. Intra-blood-brain-barrier synthesis of HTLV-III-specific IgG in patients with neurologic symptoms associated with AIDS or AIDS-related complex. N Engl J Med. 1985 Dec 12;313(24):1498–1504. doi: 10.1056/NEJM198512123132402. [DOI] [PubMed] [Google Scholar]
  31. Sarngadharan M. G., Popovic M., Bruch L., Schüpbach J., Gallo R. C. Antibodies reactive with human T-lymphotropic retroviruses (HTLV-III) in the serum of patients with AIDS. Science. 1984 May 4;224(4648):506–508. doi: 10.1126/science.6324345. [DOI] [PubMed] [Google Scholar]
  32. Schnittman S. M., Lane H. C., Higgins S. E., Folks T., Fauci A. S. Direct polyclonal activation of human B lymphocytes by the acquired immune deficiency syndrome virus. Science. 1986 Sep 5;233(4768):1084–1086. doi: 10.1126/science.3016902. [DOI] [PubMed] [Google Scholar]
  33. Shaw G. M., Harper M. E., Hahn B. H., Epstein L. G., Gajdusek D. C., Price R. W., Navia B. A., Petito C. K., O'Hara C. J., Groopman J. E. HTLV-III infection in brains of children and adults with AIDS encephalopathy. Science. 1985 Jan 11;227(4683):177–182. doi: 10.1126/science.2981429. [DOI] [PubMed] [Google Scholar]
  34. Yarchoan R., Redfield R. R., 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. doi: 10.1172/JCI112595. [DOI] [PMC free article] [PubMed] [Google Scholar]

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