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. 1986 Aug;65(2):434–442.

Analysis of IgG subclass production in cell cultures from IgA deficient patients and in normal controls as a function of age.

G Luzi, H Kubagawa, M J Crain, M D Cooper
PMCID: PMC1542324  PMID: 3791704

Abstract

IgA deficient individuals may also have low serum levels of IgG subclasses, especially IgG2. In the present study we examined the development of plasma cells producing IgM, IgA or IgG, and the IgG1 and IgG2 subclasses, following lipopolysaccharide (LPS) and pokeweed mitogen (PWM) stimulation of mononuclear cells (MNC) from normal and IgA deficient individuals as a function of age. Studies of blood MNC from 38 normal donors (age range 2-44 years) revealed an age-related distribution pattern of mu, gamma, alpha, gamma 1 and gamma 2 plasma cells produced in mitogen-stimulated and control cultures. Decreased IgA responses to both LPS and PWM were consistently observed in cultures of MNC from all of the nine children with IgA deficiency. When compared with age-matched controls the IgG response was also diminished in PWM stimulated cultures, whereas the IgM responses were normal. The IgG deficit was due to reduced responses for the gamma 1 and gamma 2 subclasses, and was most pronounced for IgG2; IgG2 plasma cell differentiation was particularly depressed in LPS cultures. In contrast to normal adult cells, blood MNC from the nine children with IgA deficiency and age-matched controls (2-17 years) yielded more IgG1 than IgG2 plasma cells in both control and LPS cultures, while the pattern of response to PWM was similar in all groups (gamma 1 greater than gamma 2). A good concordance was found between the level of secreted Ig in the culture supernatants and the relative number of IgM or, IgG and IgA plasma cells identified by immunofluorescence staining of cytoplasmic immunoglobulins.

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Selected References

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

  1. Ammann A. J., Hong R. Selective IgA deficiency: presentation of 30 cases and a review of the literature. Medicine (Baltimore) 1971 May;50(3):223–236. [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. Andersson U. Development of B lymphocyte function in childhood. Acta Paediatr Scand. 1985 Jul;74(4):568–573. doi: 10.1111/j.1651-2227.1985.tb11031.x. [DOI] [PubMed] [Google Scholar]
  4. Atwater J. S., Tomasi T. B., Jr Suppressor cells and IgA deficiency. Clin Immunol Immunopathol. 1978 Mar;9(3):379–384. doi: 10.1016/0090-1229(78)90110-1. [DOI] [PubMed] [Google Scholar]
  5. Bachmann R. Studies on the serum gamma-A-globulin level. 3. The frequency of A-gamma-A-globulinemia. Scand J Clin Lab Invest. 1965;17(4):316–320. doi: 10.3109/00365516509077057. [DOI] [PubMed] [Google Scholar]
  6. Buckley R. H. Clinical and immunologic features of selective IgA deficiency. Birth Defects Orig Artic Ser. 1975;11(1):134–142. [PubMed] [Google Scholar]
  7. Burgio G. R., Duse M., Monafo V., Ascione A., Nespoli L. Selective IgA deficiency: clinical and immunological evaluation of 50 pediatric patients. Eur J Pediatr. 1980 Mar;133(2):101–106. doi: 10.1007/BF00441577. [DOI] [PubMed] [Google Scholar]
  8. Cassidy J. T., Nordby G. L. Human serum immunoglobulin concentrations: prevalence of immunoglobulin deficiencies. J Allergy Clin Immunol. 1975 Jan;55(1):35–48. doi: 10.1016/s0091-6749(75)80006-6. [DOI] [PubMed] [Google Scholar]
  9. Cassidy J. T., Oldham G., Platts-Mills T. A. Functional assessment of a B cell defect in patients with selective IgA deficiency. Clin Exp Immunol. 1979 Feb;35(2):296–305. [PMC free article] [PubMed] [Google Scholar]
  10. Chen W. Y., Fudenberg H. H., Ades E. W. Polyclonal activation of human peripheral blood B lymphocytes by formaldehyde-fixed Salmonella paratyphi B. II. Heterogeneity of B lymphocytes. Scand J Immunol. 1982 Mar;15(3):249–257. doi: 10.1111/j.1365-3083.1982.tb00646.x. [DOI] [PubMed] [Google Scholar]
  11. Cooper M. D., Haber P., Gathings W. E., Mayumi M., Kuritani T., Briles D. E. Deficient IgA synthesis viewed in the context of normal development of IgA B-cells. Ann N Y Acad Sci. 1983 Jun 30;409:461–468. doi: 10.1111/j.1749-6632.1983.tb26890.x. [DOI] [PubMed] [Google Scholar]
  12. Cunningham-Rundles C., Oxelius V. A., Good R. A. IgG2 and IgG3 subclass deficiencies in selective IgA deficiency in the United States. Birth Defects Orig Artic Ser. 1983;19(3):173–175. [PubMed] [Google Scholar]
  13. De la Concha E. G., Subiza J. L., Fontán G., Pascual-Salcedo D., Sequí J., Bootello A. Disorders of regulatory T cells in patients with selective IgA deficiency and its relationship to associated autoimmune phenomena. Clin Exp Immunol. 1982 Aug;49(2):410–418. [PMC free article] [PubMed] [Google Scholar]
  14. Gathings W. E., Lawton A. R., Cooper M. D. Immunofluorescent studies of the development of pre-B cells, B lymphocytes and immunoglobulin isotype diversity in humans. Eur J Immunol. 1977 Nov;7(11):804–810. doi: 10.1002/eji.1830071112. [DOI] [PubMed] [Google Scholar]
  15. Goldberg L. S., Barnett E. V., Fudenberg H. H. Selective absence of IgA: a family study. J Lab Clin Med. 1968 Aug;72(2):204–212. [PubMed] [Google Scholar]
  16. Hayakawa H., Iwata T., Yata J., Kobayashi N. Primary immunodeficiency syndrome in Japan. I. Overview of a nationwide survey on primary immunodeficiency syndrome. J Clin Immunol. 1981 Jan;1(1):31–39. doi: 10.1007/BF00915474. [DOI] [PubMed] [Google Scholar]
  17. Heddle R. J., Kwitko A. O., Shearman D. J. Specific IgM and IgG antibodies in IgA deficiency. Clin Exp Immunol. 1980 Sep;41(3):453–458. [PMC free article] [PubMed] [Google Scholar]
  18. Inoue T., Okubo H., Kudo J., Ikuta T., Hachimine K., Shibata R., Yoshinari O., Fukada K., Yanase T. Selective IgA deficiency: analysis of Ig production in vitro. J Clin Immunol. 1984 May;4(3):235–241. doi: 10.1007/BF00914971. [DOI] [PubMed] [Google Scholar]
  19. Koistinen J. Selective IgA deficiency in blood donors. Vox Sang. 1975;29(3):192–202. doi: 10.1111/j.1423-0410.1975.tb00494.x. [DOI] [PubMed] [Google Scholar]
  20. Kubagawa H., Gathings W. E., Levitt D., Kearney J. F., Cooper M. D. Immunoglobulin isotype expression of normal pre-B cells as determined by immunofluorescence. J Clin Immunol. 1982 Oct;2(4):264–269. doi: 10.1007/BF00915065. [DOI] [PubMed] [Google Scholar]
  21. Lawton A. R., Royal S. A., Self K. S., Cooper M. D. IgA determinants on B-lymphocytes in patients with deficiency of circulating IgA. J Lab Clin Med. 1972 Jul;80(1):26–33. [PubMed] [Google Scholar]
  22. Levitt D., Cooper M. D. Immunoregulatory defects in a family with selective IgA deficiency. J Pediatr. 1981 Jan;98(1):52–58. doi: 10.1016/s0022-3476(81)80532-x. [DOI] [PubMed] [Google Scholar]
  23. Luzi G., Businco L., Aiuti F. A national registry for primary immunodeficiency syndromes in Italy: a report for the period 1972-1982. Birth Defects Orig Artic Ser. 1983;19(3):161–163. [PubMed] [Google Scholar]
  24. 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]
  25. Oxelius V. A., Laurell A. B., Lindquist B., Golebiowska H., Axelsson U., Björkander J., Hanson L. A. IgG subclasses in selective IgA deficiency: importance of IgG2-IgA deficiency. N Engl J Med. 1981 Jun 11;304(24):1476–1477. doi: 10.1056/NEJM198106113042408. [DOI] [PubMed] [Google Scholar]
  26. Oxelius V. A. Quantitative and qualitative investigations of serum IgG subclasses in immunodeficiency diseases. Clin Exp Immunol. 1979 Apr;36(1):112–116. [PMC free article] [PubMed] [Google Scholar]
  27. Primary immunodeficiency diseases. Report prepared for the WHO by a scientific group on immunodeficiency. Clin Immunol Immunopathol. 1983 Sep;28(3):450–475. [PubMed] [Google Scholar]
  28. Schwartz S. A. Heavy chain-specific suppression of immunoglobulin synthesis and secretion by lymphocytes from patients with selective IgA deficiency. J Immunol. 1980 Apr;124(4):2034–2041. [PubMed] [Google Scholar]
  29. Stocker F., Ammann P., Rossi E. Selective gamma-A-globulin deficiency, with dominant autosomal inheritance in a Swiss family. Arch Dis Child. 1968 Oct;43(231):585–588. doi: 10.1136/adc.43.231.585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tedder T. F., Crain M. J., Kubagawa H., Clement L. T., Cooper M. D. Evaluation of lymphocyte differentiation in primary and secondary immunodeficiency diseases. J Immunol. 1985 Sep;135(3):1786–1791. [PubMed] [Google Scholar]
  31. Vossen J. M. Membrane-associated immunoglobulin determinants on bone marrow and blood lymphocytes in the pediatric age group and on fetal tissues. Ann N Y Acad Sci. 1975 Jun 30;254:262–279. doi: 10.1111/j.1749-6632.1975.tb29176.x. [DOI] [PubMed] [Google Scholar]
  32. Waldmann T. A., Broder S., Krakauer R., Durm M., Meade B., Goldman C. Defect in IgA secretion and in IgA specific suppressor cells in patients with selective IgA deficiency. Trans Assoc Am Physicians. 1976;89:215–224. [PubMed] [Google Scholar]
  33. Waldmann T. A., Broder S., Krakauer R., MacDermott R. P., Durm M., Goldman C., Meade B. The role of suppressor cells in the pathogenesis of common variable hypogammaglobulinemia and the immunodeficiency associated with myeloma. Fed Proc. 1976 Jul;35(9):2067–2072. [PubMed] [Google Scholar]
  34. 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]
  35. Wollheim F. A., Williams R. C., Jr Immunoglobulin studies in six kindreds of patients with adult hypogammaglobulinemia. J Lab Clin Med. 1965 Sep;66(3):433–445. [PubMed] [Google Scholar]
  36. van Furth R., Schuit H. R., Hijmans W. The immunological development of the human fetus. J Exp Med. 1965 Dec 1;122(6):1173–1188. doi: 10.1084/jem.122.6.1173. [DOI] [PMC free article] [PubMed] [Google Scholar]

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