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. 1996 May;88(1):40–48. doi: 10.1046/j.1365-2567.1996.d01-634.x

Role of interleukin-2 and interferon-gamma in inducing production of IgG subclasses in lymphocytes of human newborns.

Y Kawano 1, T Noma 1
PMCID: PMC1456469  PMID: 8707348

Abstract

Unlike lymphocytes from adults, lymphocytes from cord blood of neonates cannot synthesize immunoglobulin G (IgG) in response to pokeweed mitogen (PWM). By using this mitogen in concert with interferon-gamma (IFN-gamma), interleukin-2 (IL-2), or interleukin-6 (IL-6), we studied the induction of IgG subclass molecules in lymphocytes of human neonates. IFN-gamma induced a limited, but substantial, enhancement of IgG2 production by neonatal lymphocytes. IL-2 dose dependently increased the production of each neonatal IgG subclass, whereas IL-6 did not. However, in adult lymphocytes, and under specific conditions, IL-6 or IL-2 each increased the production of all four IgG subclasses. Early in the culture IFN-gamma synergized with IL-2 during the latter or whole culture period to enhance cord blood IgG2 levels. This finding contrasted with the adult IgG2 synthesis synergistically up-regulated by IFN-gamma and IL-6. IL-2 caused a graded increase in immunoglobulin production in neonatal lymphocytes with IgG3 being the highest and IgG2 the lowest, thus corresponding to the differential increase of serum levels of IgG3/IgG1 and IgG4/IgG2 early in childhood. Results suggest that IL-2, but not IL-6, is critical to the development of human IgG subclass production.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amoroso K., Lipsky P. E. Frequency of human B cells that differentiate in response to anti-CD3-activated T cells. J Immunol. 1990 Nov 15;145(10):3155–3161. [PubMed] [Google Scholar]
  2. Andersson B., Skoglund A. C., Rönnholm M., Lindsten T., Lamon E. W., Collisson E. W., Walia A. S. Functional aspects of IgM and IgG Fc receptors on murine T lymphocytes. Immunol Rev. 1981;56:5–50. doi: 10.1111/j.1600-065x.1981.tb01046.x. [DOI] [PubMed] [Google Scholar]
  3. Barrett D. J., Ayoub E. M. IgG2 subclass restriction of antibody to pneumococcal polysaccharides. Clin Exp Immunol. 1986 Jan;63(1):127–134. [PMC free article] [PubMed] [Google Scholar]
  4. Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
  5. Calvert J. E., Johnstone R., Duggan-Keen M. F., Bird P. Immunoglobulin G subclasses secreted by human B cells in vitro in response to interleukin-2 and polyclonal activators. Immunology. 1990 Jun;70(2):162–167. [PMC free article] [PubMed] [Google Scholar]
  6. Clement L. T., Vink P. E., Bradley G. E. Novel immunoregulatory functions of phenotypically distinct subpopulations of CD4+ cells in the human neonate. J Immunol. 1990 Jul 1;145(1):102–108. [PubMed] [Google Scholar]
  7. Durandy A., Fischer A., Griscelli C. Active suppression of B lymphocyte maturation by two different newborn T lymphocyte subsets. J Immunol. 1979 Dec;123(6):2644–2650. [PubMed] [Google Scholar]
  8. Ehlers S., Smith K. A. Differentiation of T cell lymphokine gene expression: the in vitro acquisition of T cell memory. J Exp Med. 1991 Jan 1;173(1):25–36. doi: 10.1084/jem.173.1.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Freijd A., Hammarström L., Persson M. A., Smith C. I. Plasma anti-pneumococcal antibody activity of the IgG class and subclasses in otitis prone children. Clin Exp Immunol. 1984 May;56(2):233–238. [PMC free article] [PubMed] [Google Scholar]
  10. GREY H. M., KUNKEL H. G. H CHAIN SUBGROUPS OF MYELOMA PROTEINS AND NORMAL 7S GAMMA-GLOBULIN. J Exp Med. 1964 Aug 1;120:253–266. doi: 10.1084/jem.120.2.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gajewski T. F., Schell S. R., Nau G., Fitch F. W. Regulation of T-cell activation: differences among T-cell subsets. Immunol Rev. 1989 Oct;111:79–110. doi: 10.1111/j.1600-065x.1989.tb00543.x. [DOI] [PubMed] [Google Scholar]
  12. Gathings W. E., Kubagawa H., Cooper M. D. A distinctive pattern of B cell immaturity in perinatal humans. Immunol Rev. 1981;57:107–126. doi: 10.1111/j.1600-065x.1981.tb00444.x. [DOI] [PubMed] [Google Scholar]
  13. Hayward A. R., Lawton A. R. Induction of plasma cell differentiation of human fetal lymphocytes: evidence for functional immaturity of T and B cells. J Immunol. 1977 Oct;119(4):1213–1217. [PubMed] [Google Scholar]
  14. Itoh K., Inoue T., Ito K., Hirohata S. The interplay of interleukin-10 (IL-10) and interleukin-2 (IL-2) in humoral immune responses: IL-10 synergizes with IL-2 to enhance responses of human B lymphocytes in a mechanism which is different from upregulation of CD25 expression. Cell Immunol. 1994 Sep;157(2):478–488. doi: 10.1006/cimm.1994.1243. [DOI] [PubMed] [Google Scholar]
  15. Jelinek D. F., Splawski J. B., Lipsky P. E. The roles of interleukin 2 and interferon-gamma in human B cell activation, growth and differentiation. Eur J Immunol. 1986 Aug;16(8):925–932. doi: 10.1002/eji.1830160809. [DOI] [PubMed] [Google Scholar]
  16. Kawano Y., Noma T., Kou K., Yoshizawa I., Yata J. Regulation of human IgG subclass production by cytokines: human IgG subclass production enhanced differentially by interleukin-6. Immunology. 1995 Feb;84(2):278–284. [PMC free article] [PubMed] [Google Scholar]
  17. Kawano Y., Noma T., Yata J. Regulation of human IgG subclass production by cytokines. IFN-gamma and IL-6 act antagonistically in the induction of human IgG1 but additively in the induction of IgG2. J Immunol. 1994 Dec 1;153(11):4948–4958. [PubMed] [Google Scholar]
  18. Kishimoto T., Taga T., Akira S. Cytokine signal transduction. Cell. 1994 Jan 28;76(2):253–262. doi: 10.1016/0092-8674(94)90333-6. [DOI] [PubMed] [Google Scholar]
  19. Lewis D. B., Larsen A., Wilson C. B. Reduced interferon-gamma mRNA levels in human neonates. Evidence for an intrinsic T cell deficiency independent of other genes involved in T cell activation. J Exp Med. 1986 Apr 1;163(4):1018–1023. doi: 10.1084/jem.163.4.1018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lewis D. B., Yu C. C., Meyer J., English B. K., Kahn S. J., Wilson C. B. Cellular and molecular mechanisms for reduced interleukin 4 and interferon-gamma production by neonatal T cells. J Clin Invest. 1991 Jan;87(1):194–202. doi: 10.1172/JCI114970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lundgren M., Persson U., Larsson P., Magnusson C., Smith C. I., Hammarström L., Severinson E. Interleukin 4 induces synthesis of IgE and IgG4 in human B cells. Eur J Immunol. 1989 Jul;19(7):1311–1315. doi: 10.1002/eji.1830190724. [DOI] [PubMed] [Google Scholar]
  22. Lê thi Bich-Thuy, Fauci A. S. Direct effect of interleukin 2 on the differentiation of human B cells which have not been preactivated in vitro. Eur J Immunol. 1985 Nov;15(11):1075–1079. doi: 10.1002/eji.1830151102. [DOI] [PubMed] [Google Scholar]
  23. Mayumi M., Kuritani T., Kubagawa H., Cooper M. D. IgG subclass expression by human B lymphocytes and plasma cells: B lymphocytes precommitted to IgG subclass can be preferentially induced by polyclonal mitogens with T cell help. J Immunol. 1983 Feb;130(2):671–677. [PubMed] [Google Scholar]
  24. Miller K. M., Pittard W. B., Sorensen R. U. Cord blood B cell differentiation. Synergistic effect of pokeweed mitogen and Staphylococcus aureus on in vitro differentiation of B cells from human neonates. Clin Exp Immunol. 1984 May;56(2):415–424. [PMC free article] [PubMed] [Google Scholar]
  25. Miyawaki T., Seki H., Kubo M., Taniguchi N. Suppressor activity of T lymphocytes from infants assessed by co-culture with unfractionated adult lymphocytes in the pokeweed mitogen system. J Immunol. 1979 Sep;123(3):1092–1096. [PubMed] [Google Scholar]
  26. Morell A., Skvaril F., Hitzig W. H., Barandun S. IgG subclasses: development of the serum concentrations in "normal" infants and children. J Pediatr. 1972 Jun;80(6):960–964. doi: 10.1016/s0022-3476(72)80007-6. [DOI] [PubMed] [Google Scholar]
  27. Morell A., Van Loghem E., Nef M., Theilkaes L., Skvaril F. Determination of IgG subclasses and Gm allotypes in culture supernatants of pokeweed mitogen-stimulated human blood lymphocytes. J Immunol. 1981 Sep;127(3):1099–1102. [PubMed] [Google Scholar]
  28. Morito T., Bankhurst A. D., Williams R. C., Jr Studies of human cord blood and adult lymphocyte interactions with in vitro immunoglobulin production. J Clin Invest. 1979 Oct;64(4):990–995. doi: 10.1172/JCI109565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Natvig J. B., Førre O. The initial recognition of IgG subclasses. Monogr Allergy. 1986;19:1–6. [PubMed] [Google Scholar]
  30. Nonoyama S., Farrington M. L., Ochs H. D. Effect of IL-2 on immunoglobulin production by anti-CD40-activated human B cells: synergistic effect with IL-10 and antagonistic effect with IL-4. Clin Immunol Immunopathol. 1994 Sep;72(3):373–379. doi: 10.1006/clin.1994.1155. [DOI] [PubMed] [Google Scholar]
  31. Oldstone M. B., Tishon A., Moretta L. Active thymus derived suppressor lymphocytes in human cord blood. Nature. 1977 Sep 22;269(5626):333–335. doi: 10.1038/269333a0. [DOI] [PubMed] [Google Scholar]
  32. Oxelius V. A. IgG subclass levels in infancy and childhood. Acta Paediatr Scand. 1979 Jan;68(1):23–27. doi: 10.1111/j.1651-2227.1979.tb04424.x. [DOI] [PubMed] [Google Scholar]
  33. Pabst H. F., Kreth H. W. Ontogeny of the immune response as a basis of childhood disease. J Pediatr. 1980 Oct;97(4):519–534. doi: 10.1016/s0022-3476(80)80003-5. [DOI] [PubMed] [Google Scholar]
  34. Punnonen J. The role of interleukin 2 in the regulation of proliferation and IgM synthesis of human newborn mononuclear cells. Clin Exp Immunol. 1989 Mar;75(3):421–426. [PMC free article] [PubMed] [Google Scholar]
  35. Ralph P., Jeong G., Welte K., Mertelsmann R., Rabin H., Henderson L. E., Souza L. M., Boone T. C., Robb R. J. Stimulation of immunoglobulin secretion in human B lymphocytes as a direct effect of high concentrations of IL 2. J Immunol. 1984 Nov;133(5):2442–2445. [PubMed] [Google Scholar]
  36. Romagnani S., Del Prete G., Giudizi M. G., Biagiotti R., Almerigogna F., Tiri A., Alessi A., Mazzetti M., Ricci M. Direct induction of human B-cell differentiation by recombinant interleukin-2. Immunology. 1986 May;58(1):31–35. [PMC free article] [PubMed] [Google Scholar]
  37. Ruuskanen O., Pittard W. B., 3rd, Miller K., Pierce G., Sorensen R. U., Polmar S. H. Staphylococcus aureus Cowan I-induced immunoglobulin production in human cord blood lymphocytes. J Immunol. 1980 Jul;125(1):411–413. [PubMed] [Google Scholar]
  38. Scott M. G., Nahm M. H. Mitogen-induced human IgG subclass expression. J Immunol. 1984 Nov;133(5):2454–2460. [PubMed] [Google Scholar]
  39. Seppälä I. J., Routonen N., Sarnesto A., Mattila P. A., Mäkelä O. The percentages of six immunoglobulin isotypes in human antibodies to tetanus toxoid: standardization of isotype-specific second antibodies in solid-phase assay. Eur J Immunol. 1984 Sep;14(9):868–875. doi: 10.1002/eji.1830140918. [DOI] [PubMed] [Google Scholar]
  40. Shackelford P. G., Nelson S. J., Palma A. T., Nahm M. H. Human antibodies to group A streptococcal carbohydrate. Ontogeny, subclass restriction, and clonal diversity. J Immunol. 1988 May 1;140(9):3200–3205. [PubMed] [Google Scholar]
  41. Splawski J. B., Lipsky P. E. Cytokine regulation of immunoglobulin secretion by neonatal lymphocytes. J Clin Invest. 1991 Sep;88(3):967–977. doi: 10.1172/JCI115400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Splawski J. B., McAnally L. M., Lipsky P. E. IL-2 dependence of the promotion of human B cell differentiation by IL-6 (BSF-2). J Immunol. 1990 Jan 15;144(2):562–569. [PubMed] [Google Scholar]
  43. Teranishi T., Hirano T., Lin B. H., Onoue K. Demonstration of the involvement of interleukin 2 in the differentiation of Staphylococcus aureus Cowan I-stimulated B cells. J Immunol. 1984 Dec;133(6):3062–3067. [PubMed] [Google Scholar]
  44. Tosato G., Magrath I. T., Koski I. R., Dooley N. J., Blaese R. M. B cell differentiation and immunoregulatory T cell function in human cord blood lymphocytes. J Clin Invest. 1980 Aug;66(2):383–388. doi: 10.1172/JCI109867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Tucci A., Mouzaki A., James H., Bonnefoy J. Y., Zubler R. H. Are cord blood B cells functionally mature? Clin Exp Immunol. 1991 Jun;84(3):389–394. [PMC free article] [PubMed] [Google Scholar]
  46. Walker L., Johnson G. D., MacLennan I. C. The IgG subclass responses of human lymphocytes to B-cell activators. Immunology. 1983 Oct;50(2):269–272. [PMC free article] [PubMed] [Google Scholar]
  47. Wu L. Y., Blanco A., Cooper M. D., Lawton A. R. Ontogeny of B-lymphocyte differentiation induced by pokeweed mitogen. Clin Immunol Immunopathol. 1976 Mar;5(2):208–217. doi: 10.1016/0090-1229(76)90026-x. [DOI] [PubMed] [Google Scholar]
  48. Xia X., Lee H. K., Clark S. C., Choi Y. S. Recombinant interleukin (IL) 2-induced human B cell differentiation is mediated by autocrine IL6. Eur J Immunol. 1989 Dec;19(12):2275–2281. doi: 10.1002/eji.1830191215. [DOI] [PubMed] [Google Scholar]
  49. Yount W. J., Dorner M. M., Kunkel H. G., Kabat E. A. Studies on human antibodies. VI. Selective variations in subgroup composition and genetic markers. J Exp Med. 1968 Mar 1;127(3):633–646. doi: 10.1084/jem.127.3.633. [DOI] [PMC free article] [PubMed] [Google Scholar]

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