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. 1991 Feb;87(2):545–553. doi: 10.1172/JCI115029

Delineation of the functional capacity of human neonatal lymphocytes.

J B Splawski 1, D F Jelinek 1, P E Lipsky 1
PMCID: PMC296342  PMID: 1825090

Abstract

Neonatal T cell-B cell collaboration was investigated utilizing a system of T cell-dependent polyclonal B cell activation and Ig secretion. In this system, T cells activated by immobilized anti-CD3 provide a potent stimulus for Ig production by adult lymphocytes. By contrast, anti-CD3 stimulation of cord blood lymphocytes generated minimal numbers of Ig-secreting cells. Ig production by neonatal lymphocytes was enhanced by the addition of Staphylococcus aureus or secreted factors from mitogen-stimulated adult T cells. Supplementation with IL-2 resulted in the production of large amounts of IgM and small amounts of IgG and IgA, with less Ig produced than by comparable cultures of adult lymphocytes. Neonatal T cells proliferated and produced IL-2 in response to immobilized anti-CD3, and supported B cell proliferation and Ig secretion by adult B cells, although not as effectively as adult T cells. Supernatants from activated neonatal T cells were markedly limited in their capacity to support Ig production by adult B cells. Neonatal B cells could be induced to differentiate in response to anti-CD3-stimulated adult T cells. However, the amounts of IgG and IgA secreted were small compared to adult levels. These studies indicate a relative, but not absolute, functional deficiency of both neonatal B and T cells.

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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 U., Bird A. G., Britton B. S., Palacios R. Humoral and cellular immunity in humans studied at the cell level from birth to two years of age. Immunol Rev. 1981;57:1–38. doi: 10.1111/j.1600-065x.1981.tb00440.x. [DOI] [PubMed] [Google Scholar]
  3. Baroja M. L., Ceuppens J. L. More exact quantification of interleukin-2 production by addition of anti-Tac monoclonal antibody to cultures of stimulated lymphocytes. J Immunol Methods. 1987 Apr 16;98(2):267–270. doi: 10.1016/0022-1759(87)90014-7. [DOI] [PubMed] [Google Scholar]
  4. Bertotto A., Gerli R., Lanfrancone L., Crupi S., Arcangeli C., Cernetti C., Spinozzi F., Rambotti P. Activation of cord T lymphocytes. II. Cellular and molecular analysis of the defective response induced by anti-CD3 monoclonal antibody. Cell Immunol. 1990 May;127(2):247–259. doi: 10.1016/0008-8749(90)90130-j. [DOI] [PubMed] [Google Scholar]
  5. Budd R. C., Cerottini J. C., MacDonald H. R. Selectively increased production of interferon-gamma by subsets of Lyt-2+ and L3T4+ T cells identified by expression of Pgp-1. J Immunol. 1987 Jun 1;138(11):3583–3586. [PubMed] [Google Scholar]
  6. Byrne J. A., Butler J. L., Cooper M. D. Differential activation requirements for virgin and memory T cells. J Immunol. 1988 Nov 15;141(10):3249–3257. [PubMed] [Google Scholar]
  7. 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]
  8. Cheng H., Sehon A. H., Delespesse G. Human cord blood suppressor T lymphocytes: I. Phenotype and target of the inducer of suppressor cell factor. Am J Reprod Immunol Microbiol. 1985 Nov;9(3):93–99. doi: 10.1111/j.1600-0897.1985.tb00284.x. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Fairfax C. A., Borzy M. S. Interleukin 2 production, proliferative response, and receptor expression by cord blood mononuclear cells. J Clin Lab Immunol. 1988 Oct;27(2):63–67. [PubMed] [Google Scholar]
  11. Gadol N., Ault K. A. Phenotypic and functional characterization of human Leu1 (CD5) B cells. Immunol Rev. 1986 Oct;93:23–34. doi: 10.1111/j.1600-065x.1986.tb01500.x. [DOI] [PubMed] [Google Scholar]
  12. Galili U., Schlesinger M. The formation of stable E rosettes after neuraminidase treatment of either human peripheral blood lymphocytes or of sheep red blood cells. J Immunol. 1974 May;112(5):1628–1634. [PubMed] [Google Scholar]
  13. 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]
  14. Geppert T. D., Lipsky P. E. Accessory cell independent proliferation of human T4 cells stimulated by immobilized monoclonal antibodies to CD3. J Immunol. 1987 Mar 15;138(6):1660–1666. [PubMed] [Google Scholar]
  15. Gerli R., Bertotto A., Crupi S., Arcangeli C., Marinelli I., Spinozzi F., Cernetti C., Angelella P., Rambotti P. Activation of cord T lymphocytes. I. Evidence for a defective T cell mitogenesis induced through the CD2 molecule. J Immunol. 1989 Apr 15;142(8):2583–2589. [PubMed] [Google Scholar]
  16. Gerli R., Bertotto A., Spinozzi F., Cernetti C., Grignani F., Rambotti P. Phenotypic dissection of cord blood immunoregulatory T-cell subsets by using a two-color immunofluorescence study. Clin Immunol Immunopathol. 1986 Sep;40(3):429–435. doi: 10.1016/0090-1229(86)90187-x. [DOI] [PubMed] [Google Scholar]
  17. Granoff D. M., Shackelford P. G., Suarez B. K., Nahm M. H., Cates K. L., Murphy T. V., Karasic R., Osterholm M. T., Pandey J. P., Daum R. S. Hemophilus influenzae type B disease in children vaccinated with type B polysaccharide vaccine. N Engl J Med. 1986 Dec 18;315(25):1584–1590. doi: 10.1056/NEJM198612183152505. [DOI] [PubMed] [Google Scholar]
  18. Hardy R. R., Hayakawa K., Shimizu M., Yamasaki K., Kishimoto T. Rheumatoid factor secretion from human Leu-1+ B cells. Science. 1987 Apr 3;236(4797):81–83. doi: 10.1126/science.3105057. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Hayward A. R., Lydyard P. M. B cell function in the newborn. Pediatrics. 1979 Nov;64(5 Pt 2 Suppl):758–764. [PubMed] [Google Scholar]
  21. Hirohata S., Davis L. S., Lipsky P. E. Role of IL-2 in the generation of CD4+ suppressors of human B cell responsiveness. J Immunol. 1989 May 1;142(9):3104–3112. [PubMed] [Google Scholar]
  22. Hirohata S., Jelinek D. F., Lipsky P. E. T cell-dependent activation of B cell proliferation and differentiation by immobilized monoclonal antibodies to CD3. J Immunol. 1988 Jun 1;140(11):3736–3744. [PubMed] [Google Scholar]
  23. Hirohata S., Lipsky P. E. T cell regulation of human B cell proliferation and differentiation. Regulatory influences of CD45R+ and CD45R- T4 cell subsets. J Immunol. 1989 Apr 15;142(8):2597–2607. [PubMed] [Google Scholar]
  24. Jelinek D. F., Lipsky P. E. The roles of T cell factors in activation, cell cycle progression, and differentiation of human B cells. J Immunol. 1985 Mar;134(3):1690–1701. [PubMed] [Google Scholar]
  25. Jelinek D. F., Splawski J. B., Lipsky P. E. Human peripheral blood B lymphocyte subpopulations: functional and phenotypic analysis of surface IgD positive and negative subsets. J Immunol. 1986 Jan;136(1):83–92. [PubMed] [Google Scholar]
  26. 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]
  27. Kibler R., Hicks M. J., Wright A. L., Taussig L. M. A comparative analysis of cord blood and adult lymphocytes: interleukin-2 and interferon production, natural killer cell activity, and lymphocyte populations. Diagn Immunol. 1986;4(4):201–208. [PubMed] [Google Scholar]
  28. Kingsley G., Pitzalis C., Waugh A. P., Panayi G. S. Correlation of immunoregulatory function with cell phenotype in cord blood lymphocytes. Clin Exp Immunol. 1988 Jul;73(1):40–45. [PMC free article] [PubMed] [Google Scholar]
  29. Kung P., Goldstein G., Reinherz E. L., Schlossman S. F. Monoclonal antibodies defining distinctive human T cell surface antigens. Science. 1979 Oct 19;206(4416):347–349. doi: 10.1126/science.314668. [DOI] [PubMed] [Google Scholar]
  30. Kuritani T., Cooper M. D. Human B cell differentiation. II. Pokeweed mitogen-responsive B cells belong to a surface immunoglobulin D-negative subpopulation. J Exp Med. 1982 May 1;155(5):1561–1566. doi: 10.1084/jem.155.5.1561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Käyhty H., Karanko V., Peltola H., Mäkelä P. H. Serum antibodies after vaccination with Haemophilus influenzae type b capsular polysaccharide and responses to reimmunization: no evidence of immunologic tolerance or memory. Pediatrics. 1984 Nov;74(5):857–865. [PubMed] [Google Scholar]
  32. Miyawaki T., Moriya N., Nagaoki T., Taniguchi N. Maturation of B-cell differentiation ability and T-cell regulatory function in infancy and childhood. Immunol Rev. 1981;57:61–87. doi: 10.1111/j.1600-065x.1981.tb00442.x. [DOI] [PubMed] [Google Scholar]
  33. Morimoto C., Letvin N. L., Distaso J. A., Aldrich W. R., Schlossman S. F. The isolation and characterization of the human suppressor inducer T cell subset. J Immunol. 1985 Mar;134(3):1508–1515. [PubMed] [Google Scholar]
  34. Notarangelo L. D., Panina P., Imberti L., Malfa P., Ugazio A. G., Albertini A. Neonatal T4+ lymphocytes: analysis of the expression of 4B4 and 2H4 antigens. Clin Immunol Immunopathol. 1988 Jan;46(1):61–67. doi: 10.1016/0090-1229(88)90006-2. [DOI] [PubMed] [Google Scholar]
  35. Olding L. B., Murgita R. A., Wigzell H. Mitogen-stimulated lymphoid cells from human newborns suppress the proliferation of maternal lymphocytes actoss a cell-impermeable membrane. J Immunol. 1977 Sep;119(3):1109–1114. [PubMed] [Google Scholar]
  36. 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]
  37. Papadogiannakis N., Johnsen S. A., Olding L. B. Human fetal/neonatal suppressor activity: relation between OKT phenotypes and sensitivity to prostaglandin E2 in maternal and neonatal lymphocytes. Am J Reprod Immunol Microbiol. 1985 Dec;9(4):105–110. doi: 10.1111/j.1600-0897.1985.tb00287.x. [DOI] [PubMed] [Google Scholar]
  38. Papadogiannakis N., Johnsen S. A., Olding L. B. Monocyte-regulated hyporesponsiveness of human cord blood lymphocytes to OKT3-monoclonal-antibody-induced mitogenesis. Scand J Immunol. 1986 Jan;23(1):91–99. doi: 10.1111/j.1365-3083.1986.tb01946.x. [DOI] [PubMed] [Google Scholar]
  39. Powers G. D., Abbas A. K., Miller R. A. Frequencies of IL-2- and IL-4-secreting T cells in naive and antigen-stimulated lymphocyte populations. J Immunol. 1988 May 15;140(10):3352–3357. [PubMed] [Google Scholar]
  40. Rosenberg S. A., Lipsky P. E. Monocyte dependence of pokeweed mitogen-induced differentiation of immunoglobulin-secreting cells from human peripheral blood mononuclear cells. J Immunol. 1979 Mar;122(3):926–931. [PubMed] [Google Scholar]
  41. 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]
  42. Saiki O., Ralph P. IgM- and IgD-bearing peripheral blood lymphocytes differentiate to IgM but not IgG or IgA immunoglobulin-secreting cells. Eur J Immunol. 1982 Jun;12(6):506–510. doi: 10.1002/eji.1830120611. [DOI] [PubMed] [Google Scholar]
  43. Saiki O., Ralph P. Induction of human immunoglobulin secretion. I. Synergistic effect of B cell mitogen Cowan I plus T cell mitogens or factors. J Immunol. 1981 Sep;127(3):1044–1047. [PubMed] [Google Scholar]
  44. Salmon M., Kitas G. D., Bacon P. A. Production of lymphokine mRNA by CD45R+ and CD45R- helper T cells from human peripheral blood and by human CD4+ T cell clones. J Immunol. 1989 Aug 1;143(3):907–912. [PubMed] [Google Scholar]
  45. Sanders M. E., Makgoba M. W., Sharrow S. O., Stephany D., Springer T. A., Young H. A., Shaw S. Human memory T lymphocytes express increased levels of three cell adhesion molecules (LFA-3, CD2, and LFA-1) and three other molecules (UCHL1, CDw29, and Pgp-1) and have enhanced IFN-gamma production. J Immunol. 1988 Mar 1;140(5):1401–1407. [PubMed] [Google Scholar]
  46. Splawski J. B., Jelinek D. F., Lipsky P. E. Immunomodulatory role of IL-4 on the secretion of Ig by human B cells. J Immunol. 1989 Mar 1;142(5):1569–1575. [PubMed] [Google Scholar]
  47. Steel C. M., Philipson J., Arthur E., Gardiner S. E., Newton M. S., McIntosh R. V. Possibility of EB virus preferentially transforming a subpopulation of human B lymphocytes. Nature. 1977 Dec 22;270(5639):729–731. doi: 10.1038/270729a0. [DOI] [PubMed] [Google Scholar]
  48. Tadmori W., Feingersh D., Clark S. C., Choi Y. S. Human recombinant IL-3 stimulates B cell differentiation. J Immunol. 1989 Mar 15;142(6):1950–1955. [PubMed] [Google Scholar]
  49. Tedder T. F., Clement L. T., Cooper M. D. Human lymphocyte differentiation antigens HB-10 and HB-11. I. Ontogeny of antigen expression. J Immunol. 1985 May;134(5):2983–2988. [PubMed] [Google Scholar]
  50. Thiele D. L., Kurosaka M., Lipsky P. E. Phenotype of the accessory cell necessary for mitogen-stimulated T and B cell responses in human peripheral blood: delineation by its sensitivity to the lysosomotropic agent, L-leucine methyl ester. J Immunol. 1983 Nov;131(5):2282–2290. [PubMed] [Google Scholar]
  51. Thiele D. L., Lipsky P. E. Modulation of human natural killer cell function by L-leucine methyl ester: monocyte-dependent depletion from human peripheral blood mononuclear cells. J Immunol. 1985 Feb;134(2):786–793. [PubMed] [Google Scholar]
  52. 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]
  53. Uchiyama T., Broder S., Waldmann T. A. A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. I. Production of anti-Tac monoclonal antibody and distribution of Tac (+) cells. J Immunol. 1981 Apr;126(4):1393–1397. [PubMed] [Google Scholar]
  54. 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]
  55. Wysocki L. J., Sato V. L. "Panning" for lymphocytes: a method for cell selection. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2844–2848. doi: 10.1073/pnas.75.6.2844. [DOI] [PMC free article] [PubMed] [Google Scholar]

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