Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1992 Feb;87(2):237–245. doi: 10.1111/j.1365-2249.1992.tb02981.x

Subclass composition and J-chain expression of the 'compensatory' gastrointestinal IgG cell population in selective IgA deficiency.

D E Nilssen 1, P Brandtzaeg 1, S S Frøland 1, O Fausa 1
PMCID: PMC1554248  PMID: 1735187

Abstract

The subclass distribution of IgG-producing immunocytes was examined by two-colour immunohistochemistry in gastrointestinal mucosa of 14 patients with selective serum IgA deficiency providing the following biopsy material: gastric (n = 1); jejunal (n = 12); colonic (n = 1); and rectal (n = 2). All except two patients suffered from various infections, and coeliac disease was observed in six of them. Control reference data were based on biopsies from immunologically intact subjects, including histologically normal jejunal (n = 10) and large bowel (n = 10) mucosa and stomach mucosa with slight chronic gastritis (n = 8). The total mucosal population of immunoglobulin-producing cells per 500 microns gut length unit was only slightly decreased in IgA deficiency because of an increased number of IgG (30%) and especially IgM (71%) immunocytes. The IgG1 immunocyte proportion in the proximal gut (median 87%) was higher than that in the comparable controls (gastric 69%, jejunal 66%). A similar trend was seen in the distal gut (69%) compared with controls from the large bowel mucosa (55%). Conversely, IgG2 and IgG3 cell proportions were significantly decreased compared with the respective controls from the proximal gut. The same was true for IgG4, which also was significantly reduced in jejunal mucosa. Paired staining for cytoplasmic J chain and immunoglobulin isotype showed 71% positivity for jejunal IgG-producing cells in IgA deficiency, which was somewhat reduced compared with comparable controls (89%). J chain appeared to be preferentially expressed by IgG1 cells (75%), but was also found in IgG2 (70%), IgG3 (32%) and IgG4 cells (33%). IgM-producing cells showed a J-chain positivity (99%) in IgA deficiency similar to normal (100%). Our results suggested that the block in mucosal B cell differentiation to IgA expression in the proximal gut is mainly located immediately upstream to the CH alpha 1 gene, giving excessive terminal maturation of J-chain-positive IgG1 immunocytes.

Full text

PDF
237

Selected References

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

  1. Baklien K., Brandtzaeg P. Comparative mapping of the local distribution of immunoglobulin-containing cells in ulcerative colitis and Crohn's disease of the colon. Clin Exp Immunol. 1975 Nov;22(2):197–209. [PMC free article] [PubMed] [Google Scholar]
  2. Baklien K., Brandtzaeg P., Fausa O. Immunoglobulins in jejunal mucosa and serum from patients with adult coeliac disease. Scand J Gastroenterol. 1977;12(2):149–159. [PubMed] [Google Scholar]
  3. Bjerke K., Brandtzaeg P. Terminally differentiated human intestinal B cells. J chain expression of IgA and IgG subclass-producing immunocytes in the distal ileum compared with mesenteric and peripheral lymph nodes. Clin Exp Immunol. 1990 Nov;82(2):411–415. doi: 10.1111/j.1365-2249.1990.tb05462.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Björkander J., Bengtsson U., Oxelius V. A., Hanson L. A. Symptoms in patients with lowered levels of IgG subclasses, with or without IgA deficiency, and effects of immunoglobulin prophylaxis. Monogr Allergy. 1986;20:157–163. [PubMed] [Google Scholar]
  5. Brandtzaeg P., Baklien K., Fausa O., Hoel P. S. Immunohistochemical characterization of local immunoglobulin formation in ulcerative colitis. Gastroenterology. 1974 Jun;66(6):1123–1136. [PubMed] [Google Scholar]
  6. Brandtzaeg P., Fjellanger I., Gjeruldsen S. T. Immunoglobulin M: local synthesis and selective secretion in patients with immunoglobulin A deficiency. Science. 1968 May 17;160(3829):789–791. doi: 10.1126/science.160.3829.789. [DOI] [PubMed] [Google Scholar]
  7. Brandtzaeg P., Gjeruldsen S. T., Korsrud F., Baklien K., Berdal P., Ek J. The human secretory immune system shows striking heterogeneity with regard to involvement of J chain-positive IgD immunocytes. J Immunol. 1979 Feb;122(2):503–510. [PubMed] [Google Scholar]
  8. Brandtzaeg P., Guy-Grand D., Griscelli C. Intestinal salivary, and tonsillar IgA and J-chain production in a patient with severe deficiency of serum IgA. Scand J Immunol. 1981;13(4):313–325. doi: 10.1111/j.1365-3083.1981.tb00140.x. [DOI] [PubMed] [Google Scholar]
  9. Brandtzaeg P. Human secretory immunoglobulin M. An immunochemical and immunohistochemical study. Immunology. 1975 Sep;29(3):559–570. [PMC free article] [PubMed] [Google Scholar]
  10. Brandtzaeg P. Immunohistochemical characterization of intracellular J-chain and binding site for secretory component (SC) in human immunoglobulin (Ig)-producing cells. Mol Immunol. 1983 Sep;20(9):941–966. doi: 10.1016/0161-5890(83)90036-6. [DOI] [PubMed] [Google Scholar]
  11. Brandtzaeg P., Karlsson G., Hansson G., Petruson B., Björkander J., Hanson L. A. The clinical condition of IgA-deficient patients is related to the proportion of IgD- and IgM-producing cells in their nasal mucosa. Clin Exp Immunol. 1987 Mar;67(3):626–636. [PMC free article] [PubMed] [Google Scholar]
  12. Brandtzaeg P., Kett K., Rognum T. O., Söderström R., Björkander J., Söderström T., Petrusson B., Hanson L. A. Distribution of mucosal IgA and IgG subclass-producing immunocytes and alterations in various disorders. Monogr Allergy. 1986;20:179–194. [PubMed] [Google Scholar]
  13. Brandtzaeg P., Korsrud F. R. Significance of different J chain profiles in human tissues: generation of IgA and IgM with binding site for secretory component is related to the J chain expressing capacity of the total local immunocyte population, including IgG and IgD producing cells, and depends on the clinical state of the tissue. Clin Exp Immunol. 1984 Dec;58(3):709–718. [PMC free article] [PubMed] [Google Scholar]
  14. Brandtzaeg P. Mucosal and glandular distribution of immunoglobulin components. Immunohistochemistry with a cold ethanol-fixation technique. Immunology. 1974 Jun;26(6):1101–1114. [PMC free article] [PubMed] [Google Scholar]
  15. Brandtzaeg P., Nilssen D. E., Rognum T. O., Thrane P. S. Ontogeny of the mucosal immune system and IgA deficiency. Gastroenterol Clin North Am. 1991 Sep;20(3):397–439. [PubMed] [Google Scholar]
  16. Brandtzaeg P. Role of J chain and secretory component in receptor-mediated glandular and hepatic transport of immunoglobulins in man. Scand J Immunol. 1985 Aug;22(2):111–146. doi: 10.1111/j.1365-3083.1985.tb01866.x. [DOI] [PubMed] [Google Scholar]
  17. Brandtzaeg P. Studies on J chain and binding site for secretory component in circulating human B cells. II. The cytoplasm. Clin Exp Immunol. 1976 Jul;25(1):59–66. [PMC free article] [PubMed] [Google Scholar]
  18. Calvert J. E., Maruyama S., Tedder T. F., Webb C. F., Cooper M. D. Cellular events in the differentiation of antibody-secreting cells. Semin Hematol. 1984 Oct;21(4):226–243. [PubMed] [Google Scholar]
  19. Crabbé P. A., Heremans J. F. Lack of gamma A-immunoglobulin in serum of patients with steatorrhoea. Gut. 1966 Apr;7(2):119–127. doi: 10.1136/gut.7.2.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Esser C., Radbruch A. Immunoglobulin class switching: molecular and cellular analysis. Annu Rev Immunol. 1990;8:717–735. doi: 10.1146/annurev.iy.08.040190.003441. [DOI] [PubMed] [Google Scholar]
  21. Haber P. L., Mestecky J. J-chain expression in human cells producing IgG subclasses. Cell Immunol. 1985 Apr 1;91(2):515–519. doi: 10.1016/0008-8749(85)90249-7. [DOI] [PubMed] [Google Scholar]
  22. Hanson L. A., Björkander J., Carlsson B., Roberton D., Söderström T. The heterogeneity of IgA deficiency. J Clin Immunol. 1988 May;8(3):159–162. doi: 10.1007/BF00917561. [DOI] [PubMed] [Google Scholar]
  23. Jefferis R., Reimer C. B., Skvaril F., de Lange G., Ling N. R., Lowe J., Walker M. R., Phillips D. J., Aloisio C. H., Wells T. W. Evaluation of monoclonal antibodies having specificity for human IgG sub-classes: results of an IUIS/WHO collaborative study. Immunol Lett. 1985;10(3-4):223–252. doi: 10.1016/0165-2478(85)90082-3. [DOI] [PubMed] [Google Scholar]
  24. Kanoh T., Nishida O., Uchino H., Miyake T., Hishitani Y. Transport defect of IgM into luminal space in selective IgA deficiency. Clin Immunol Immunopathol. 1987 Sep;44(3):272–282. doi: 10.1016/0090-1229(87)90071-7. [DOI] [PubMed] [Google Scholar]
  25. Kett K., Brandtzaeg P., Fausa O. J-chain expression is more prominent in immunoglobulin A2 than in immunoglobulin A1 colonic immunocytes and is decreased in both subclasses associated with inflammatory bowel disease. Gastroenterology. 1988 Jun;94(6):1419–1425. doi: 10.1016/0016-5085(88)90681-6. [DOI] [PubMed] [Google Scholar]
  26. Kett K., Brandtzaeg P., Radl J., Haaijman J. J. Different subclass distribution of IgA-producing cells in human lymphoid organs and various secretory tissues. J Immunol. 1986 May 15;136(10):3631–3635. [PubMed] [Google Scholar]
  27. Kett K., Rognum T. O., Brandtzaeg P. Mucosal subclass distribution of immunoglobulin G-producing cells is different in ulcerative colitis and Crohn's disease of the colon. Gastroenterology. 1987 Nov;93(5):919–924. doi: 10.1016/0016-5085(87)90552-x. [DOI] [PubMed] [Google Scholar]
  28. Kim P. H., Kagnoff M. F. Transforming growth factor beta 1 increases IgA isotype switching at the clonal level. J Immunol. 1990 Dec 1;145(11):3773–3778. [PubMed] [Google Scholar]
  29. Kim P. H., Kagnoff M. F. Transforming growth factor-beta 1 is a costimulator for IgA production. J Immunol. 1990 May 1;144(9):3411–3416. [PubMed] [Google Scholar]
  30. Layton J. E., Vitetta E. S., Uhr J. W., Krammer P. H. Clonal analysis of B cells induced to secrete IgG by T cell-derived lymphokine(s). J Exp Med. 1984 Dec 1;160(6):1850–1863. doi: 10.1084/jem.160.6.1850. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. McGhee J. R., Mestecky J., Elson C. O., Kiyono H. Regulation of IgA synthesis and immune response by T cells and interleukins. J Clin Immunol. 1989 May;9(3):175–199. doi: 10.1007/BF00916814. [DOI] [PubMed] [Google Scholar]
  32. McLoughlin G. A., Hede J. E., Temple J. G., Bradley J., Chapman D. M., McFarland J. The role of IgA in the prevention of bacterial colonization of the jejunum in the vagotomized subject. Br J Surg. 1978 Jun;65(6):435–437. doi: 10.1002/bjs.1800650619. [DOI] [PubMed] [Google Scholar]
  33. Nilssen D. E., Høverstad T., Frøland S. S., Midtvedt T. Short-chain fatty acids and other intestinal microflora-associated characteristics in faeces of patients with severe B-cell immunodeficiency. Scand J Gastroenterol. 1989 Jan;24(1):21–27. doi: 10.3109/00365528909092234. [DOI] [PubMed] [Google Scholar]
  34. Nilssen D. E., Söderström R., Brandtzaeg P., Kett K., Helgeland L., Karlsson G., Söderström T., Hanson L. A. Isotype distribution of mucosal IgG-producing cells in patients with various IgG subclass deficiencies. Clin Exp Immunol. 1991 Jan;83(1):17–24. doi: 10.1111/j.1365-2249.1991.tb05581.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Papadea C., Check I. J. Human immunoglobulin G and immunoglobulin G subclasses: biochemical, genetic, and clinical aspects. Crit Rev Clin Lab Sci. 1989;27(1):27–58. doi: 10.3109/10408368909106589. [DOI] [PubMed] [Google Scholar]
  36. Richman L. K., Brown W. R. Immunochemical characterization of IgM in human intestinal fluids. J Immunol. 1977 Oct;119(4):1515–1519. [PubMed] [Google Scholar]
  37. Rognum T. O., Kett K., Fausa O., Bengtsson U., Kilander A., Scott H., Gaarder P. I., Brandtzaeg P. Raised number of jejunal IgG2-producing cells in untreated adult coeliac disease compared with food allergy. Gut. 1989 Nov;30(11):1574–1580. doi: 10.1136/gut.30.11.1574. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Savilahti E. IgA deficiency in children. Immunoglobulin-containing cells in the intestinal mucosa, immunoglobulins in secretions and serum IgA levels. Clin Exp Immunol. 1973 Mar;13(3):395–406. [PMC free article] [PubMed] [Google Scholar]
  39. Savilahti E., Klemola T., Carlsson B., Mellander L., Stenvik M., Hovi T. Inadequacy of mucosal IgM antibodies in selective IgA deficiency: excretion of attenuated polio viruses is prolonged. J Clin Immunol. 1988 Mar;8(2):89–94. doi: 10.1007/BF00917895. [DOI] [PubMed] [Google Scholar]
  40. Savilahti E., Pelkonen P. Clinical findings and intestinal immunoglobulins in children with partial IgA deficiency. Acta Paediatr Scand. 1979 Jul;68(4):513–519. doi: 10.1111/j.1651-2227.1979.tb05049.x. [DOI] [PubMed] [Google Scholar]
  41. Shimizu A., Honjo T. Immunoglobulin class switching. Cell. 1984 Apr;36(4):801–803. doi: 10.1016/0092-8674(84)90029-1. [DOI] [PubMed] [Google Scholar]
  42. Smith C. I., Möller G., Severinson E., Hammarström L. Frequencies of interleukin-5 mRNA-producing cells in healthy individuals and in immunoglobulin-deficient patients, measured by in situ hybridization. Clin Exp Immunol. 1990 Sep;81(3):417–422. doi: 10.1111/j.1365-2249.1990.tb05349.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Snapper C. M., Finkelman F. D., Paul W. E. Differential regulation of IgG1 and IgE synthesis by interleukin 4. J Exp Med. 1988 Jan 1;167(1):183–196. doi: 10.1084/jem.167.1.183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Strober W., Sneller M. C. Cellular and molecular events accompanying IgA B cell differentiation. Monogr Allergy. 1988;24:181–190. [PubMed] [Google Scholar]
  45. Söderström T., Söderström R., Bengtsson U., Björkander J., Hellstrand K., Holm J., Hanson L. A. Clinical and immunological evaluation of patients low in single or multiple IgG subclasses. Monogr Allergy. 1986;20:135–142. [PubMed] [Google Scholar]
  46. Valnes K., Brandtzaeg P. Subclass distribution of mucosal IgG-producing cells in gastritis. Gut. 1989 Mar;30(3):322–326. doi: 10.1136/gut.30.3.322. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES