Logo of clinexpimmunolLink to Publisher's site
Clin Exp Immunol. 1994 Feb; 95(2): 215–221.
PMCID: PMC1534935

Intestinal B cell defects in common variable immunodeficiency.

Abstract

The humoral immune system of the small intestine of 17 patients with common variable immunodeficiency (CVID) was studied by immunohistology using antibodies specific for IgA1,2, IgM, IgG1-4, the J chain and the secretory component (SC). IgA1,2+, IgG2+ and IgM+ lamina propria B cells were totally lacking in 65% (11/17), 41% (7/17) and 18% (3/17) of CVID patients, respectively. One patient exhibited an isolated IgA1 subclass deficiency. The proportion of plasma cells in conventionally stained histological sections of the same intestinal biopsies showed a close correlation with the numbers of IgA+ and IgM+ cells. Considerable numbers of J chain-synthesizing cells were present in all patients with CVID, indicating the presence of early B cells unable to differentiate into immunoglobulin-producing plasma cells. Most of the patients with intestinal IgA and/or IgM defects strongly expressed the SC in their enterocytes, suggesting an immunoglobulin-independent regulation of the SC. Clinically, only CVID patients with intestinal IgA defects developed intestinal infections with Giardia lamblia, Campylobacter jejuni or Candida albicans. The outcome of in vitro immunoglobulin synthesis assays with peripheral blood lymphocytes did not predict the presence or absence of the respective isotype-producing B cells in the intestinal lamina propria. Thus, immunohistological examinations of intestinal biopsies are required to determine the extent of mucosal immunodeficiency in CVID patients.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Saxon A, Giorgi JV, Sherr EH, Kagan JM. Failure of B cells in common variable immunodeficiency to transit from proliferation to differentiation is associated with altered B cell surface-molecule display. J Allergy Clin Immunol. 1989 Jul;84(1):44–55. [PubMed]
  • Kinlen LJ, Webster AD, Bird AG, Haile R, Peto J, Soothill JF, Thompson RA. Prospective study of cancer in patients with hypogammaglobulinaemia. Lancet. 1985 Feb 2;1(8423):263–266. [PubMed]
  • Cunningham-Rundles C. Clinical and immunologic analyses of 103 patients with common variable immunodeficiency. J Clin Immunol. 1989 Jan;9(1):22–33. [PubMed]
  • Hermans PE, Diaz-Buxo JA, Stobo JD. Idiopathic late-onset immunoglobulin deficiency. Clinical observations in 50 patients. Am J Med. 1976 Aug;61(2):221–237. [PubMed]
  • Bästlein C, Burlefinger R, Holzberg E, Voeth C, Garbrecht M, Ottenjann R. Common variable immunodeficiency syndrome and nodular lymphoid hyperplasia in the small intestine. Endoscopy. 1988 Sep;20(5):272–275. [PubMed]
  • Broom BC, de la Concha EG, Webster AD, Loewi G, Asherson GL. Dichotomy between immunoglobulin synthesis by cells in gut and blood of patients with hypogammaglobulinaemia. Lancet. 1975 Aug 9;2(7928):253–256. [PubMed]
  • Norton AJ, Isaacson PG. Detailed phenotypic analysis of B-cell lymphoma using a panel of antibodies reactive in routinely fixed wax-embedded tissue. Am J Pathol. 1987 Aug;128(2):225–240. [PMC free article] [PubMed]
  • Rump JA, Jahreis A, Schlesier M, Dräger R, Melchers I, Peter HH. Possible role of IL-2 deficiency for hypogammaglobulinaemia in patients with common variable immunodeficiency. Clin Exp Immunol. 1992 Aug;89(2):204–210. [PMC free article] [PubMed]
  • Brandtzaeg P, Korsrud FR. 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]
  • Ahnen DJ, Brown WR, Kloppel TM. Secretory component: the polymeric immunoglobulin receptor. What's in it for the gastroenterologist and hepatologist? Gastroenterology. 1985 Sep;89(3):667–682. [PubMed]
  • Koshland ME. The coming of age of the immunoglobulin J chain. Annu Rev Immunol. 1985;3:425–453. [PubMed]
  • Mestecky J, Russell MW. IgA subclasses. Monogr Allergy. 1986;19:277–301. [PubMed]
  • Underdown BJ, Schiff JM. Immunoglobulin A: strategic defense initiative at the mucosal surface. Annu Rev Immunol. 1986;4:389–417. [PubMed]
  • Bryant A, Calver NC, Toubi E, Webster AD, Farrant J. Classification of patients with common variable immunodeficiency by B cell secretion of IgM and IgG in response to anti-IgM and interleukin-2. Clin Immunol Immunopathol. 1990 Aug;56(2):239–248. [PubMed]
  • Nagura H, Kohler PF, Brown WR. Immunocytochemical characterization of the lymphocytes in nodular lymphoid hyperplasia of the bowel. Lab Invest. 1979 Jan;40(1):66–73. [PubMed]
  • Kelényi G. Intracellular J chains in lymphoproliferative diseases. Virchows Arch A Pathol Anat Histopathol. 1985;405(3):365–378. [PubMed]
  • Saiki O, Ralph P, Cunningham-Rundles C, Good RA. Three distinct stages of B-cell defects in common varied immunodeficiency. Proc Natl Acad Sci U S A. 1982 Oct;79(19):6008–6012. [PMC free article] [PubMed]
  • Dura WT, Bernatowska E. Secretory component, alpha 1-antitrypsin and lysozyme in IgA deficient children. An immunohistochemical evaluation of intestinal mucosa. Histopathology. 1984 Sep;8(5):747–757. [PubMed]
  • Brandtzaeg P, Nilssen DE, Rognum TO, Thrane PS. Ontogeny of the mucosal immune system and IgA deficiency. Gastroenterol Clin North Am. 1991 Sep;20(3):397–439. [PubMed]
  • Wright JJ, Wagner DK, Blaese RM, Hagengruber C, Waldmann TA, Fleisher TA. Characterization of common variable immunodeficiency: identification of a subset of patients with distinctive immunophenotypic and clinical features. Blood. 1990 Nov 15;76(10):2046–2051. [PubMed]
  • Lebranchu Y, Thibault G, Degenne D, Bardos P. Abnormalities in CD4+ T lymphocyte subsets in patients with common variable immunodeficiency. Clin Immunol Immunopathol. 1991 Oct;61(1):83–92. [PubMed]
  • Baumert E, Wolff-Vorbeck G, Schlesier M, Peter HH. Immunophenotypical alterations in a subset of patients with common variable immunodeficiency (CVID). Clin Exp Immunol. 1992 Oct;90(1):25–30. [PMC free article] [PubMed]
  • Sneller MC, Strober W. Abnormalities of lymphokine gene expression in patients with common variable immunodeficiency. J Immunol. 1990 May 15;144(10):3762–3769. [PubMed]
  • Fiedler W, Sykora KW, Welte K, Kolitz JE, Cunningham-Rundles C, Holloway K, Miller GA, Souza L, Mertelsmann R. T-cell activation defect in common variable immunodeficiency: restoration by phorbol myristate acetate (PMA) or allogeneic macrophages. Clin Immunol Immunopathol. 1987 Aug;44(2):206–218. [PubMed]
  • Van den Brande P, Geboes K, Vantrappen G, Van den Eeckhout A, Vertessen S, Stevens EA, Ceuppens JL. Intestinal nodular lymphoid hyperplasia in patients with common variable immunodeficiency: local accumulation of B and CD8(+) lymphocytes. J Clin Immunol. 1988 Jul;8(4):296–306. [PubMed]

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

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...