A limiting-dilution analysis of activated circulating B cells in Crohn's disease
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Abstract
In the present study the spontaneousin vitro production of immunoglobulins G, A, and M by peripheral mononuclear cells was evaluated, in patients with Crohn's disease, in relation to the state of B-cell activation and further characterized by limiting-dilution analysis. A total of 25 patients with Crohn's disease and 10 healthy controls was studied. The proportion of the transferrin receptor-bearing cells in the B7+ subset was higher in active Crohn's disease patients than in either those with quiescent disease or controls. There was a significant rise in thein vitro IgG, IgM, and IgA production in patients with untreated active Crohn's disease compared to either those with untreated quiescent disease or controls. When patients were followed up from the active phase to clinical remission, a significant decrease in the production of IgG and IgM was observed. IgA levels also showed a decrease, although not reaching statistical significance. When the Ig production was analyzed by limiting dilution, no difference was observed between patients and controls in terms of either precursor frequency of Ig-producing cells or patterns of frequency distribution. In both patients and controls a biphasic limiting-dilution profile was observed. This study shows that a significant B-cell activation is present in Crohn's disease patients, which is accompanied by an increase in immunoglobulin production. This study also indicates that in Crohn's disease the increased immunoglobulin production is related to an augmented B-cell clone size rather than to an increased precursor frequency.
Key words
Peripheral activated B cells immunoglobulin production limiting-dilution analysis Crohn's diseasePreview
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References
- 1.Wensick F, van de Merwe JP, Mayberry JF: An international study of agglutinins to eubacterium, peptostreptococcus and coprococcus species in Crohn's disease, ulcerative colitis and control subjects. Digestion 27:63–67, 1983Google Scholar
- 2.Blaser MJ, Miller RA, Lacher J, Singleton JW: Patients with active Crohn's disease have elevated serum antibodies of seven enteric bacterial pathogens. Gastroenterology 87:888–895, 1984Google Scholar
- 3.Paganelli R, Pallone F, Montano S, Lemoli S, Matricardi P, Fais S, Paoluzi P, D'Amelio R, Aiuti F: Isotypic analysis of antibody response to a food antigen in inflammatory bowel disease. Int Arch Appl Immunol 78:81–87, 1985Google Scholar
- 4.Pallone F, Montano S, Ricci R, Iavicoli M, Di Mario U: New evidence of circulating immunocomplexes in Crohn's disease using two sensitive methods. J Clin Lab Immunol 5:23–25, 1981Google Scholar
- 5.Pallone F, Matricardi PM, Squarcia O, Fais S, Le Moli S, Boirivant M, Paoluzi P, D'Amelio R: Raised serum levels of Ig M-rheumatoid factor and anti-F(ab')2 autoantibodies in patients with active inflammatory bowel disease. J Clin Lab Immunol 19:175–180, 1986Google Scholar
- 6.Holdstock G, Ershler WB, Krawitt EL: Defective lymphocyte IgA production in inflammatory bowel disease. Clin Immunol Immunopathol 24:47–54, 1982Google Scholar
- 7.Sieber G, Herrmann F, Zeitz M, Teichmann H, Ruhl H: Abnormalities of B-cell activation and immunoregulation in patients with Crohn's disease. Gut 25:1255–1261, 1984Google Scholar
- 8.Mac Dermott RP, Nash GS, Bertovich MJ, Seiden MV, Bragdon MJ, Beale MG: Alterations of IgM, IgG, and IgA synthesis and secretion by peripheral blood and intestinal mononuclear cells from patients with ulcerative colitis and Crohn's disease. Gastroenterology 81:844–852, 1981Google Scholar
- 9.Fais S, Pallone F, Squarcia O, Boirivant M, Pozzilli P: T cell early activation antigens expressed by peripheral lymphocytes in Crohn's disease. J Clin Lab Immunol 16:75–76, 1985Google Scholar
- 10.Pallone F, Fais S, Squarcia O, Biancone L, Pozzilli P, Boirivant M: Activation of perpheral blood and intestinal lamina propria lymphocytes in Crohn's disease. In vivo state of activation and in vitro response to stimulation as defined by the expression of early activation antigens. Gut 28:745–753, 1987Google Scholar
- 11.Auer IO, Roder A, Frohlich J: Immune status in Crohn's disease. VI. Immunoregulation evaluated by multiple, distinct T-suppressor cell assays of lymphocyte proliferation, and by enumeration of immunoregulatory T-lymphocyte subsets. Gastroenterology 86:1531–1543, 1984Google Scholar
- 12.Elson CO, Braeff AS, James SP, Strober W: Covert suppressor T cell activity in Crohn's disease. Gastroenterology 80:1513–1521, 1981Google Scholar
- 13.Lefkovits I, Waldmann H: Limiting dilution analysis of cells of immune system I. The clonal basis of the immune response. Immunol Today 5:265–268, 1984Google Scholar
- 14.Waldmann H, Lefkovits I: Limiting dilution analysis of cells of the immune system. II. What can be learned? Immunol Today 5:295–298, 1984Google Scholar
- 15.Harvey RF, Bradshaw JM: A simple index of Crohn's disease. Lancet 1:514, 1980Google Scholar
- 16.Di Mario U, Guy K: Evaluation of class II antigen positive T cells: A simple double staining method using monoclonal antibodies. J Clin Lab Immunol 13:203–204, 1984Google Scholar
- 17.Neckers LM, Yenokida G, James SP: The role of the transferrin receptor in human B lymphocyte activation. J Immunol 133:2437–2441, 1984Google Scholar
- 18.Romagnani S: Cytokines involved in activation, growth and differentiation of human B cells. J Immunol Res 1:41–51, 1989Google Scholar
- 19.Famularo G, Giacomelli R, Alesse E, Cifone MG, Morrone S, Boirivant M, Danese C, Perego MA, Santoni A, Tonietti G: Polyclonal B lymphocytes activation in progressive sistemic sclerosis. J Clin Lab Immunol, 1989 (in press)Google Scholar
- 20.Eichmann K, Falk I, Melchers I, Simon MM: Quantitative studies on T cell diversity. J Exp Med 152:477–492, 1980Google Scholar
- 21.Zoller M, Andrighetto G: Regulation of carrier-specific response via a haptenic epitope. Scand J Immunol 26:277–286, 1987Google Scholar
- 22.Dosh HM, Lam P, Guerin D: Differential regulation of activation, clonal expansion, and antibody secretion in human B cells. J Immunol 135:3808–3816, 1985Google Scholar
- 23.Cupps TR, Edgar LC, Thomas CA, Fauci AS: Multiple mechanisms of B cell immunoregulation in man after administration of “in vivo” corticosteroids. J Immunol 132:170–175, 1984Google Scholar
- 24.Cupps TR, Gerrard TL, Falkoff RJM, Whalen G, Gauci AS. Effects of “in vitro” corticosteroids on B cell activation, proliferation and differentiation. J Clin Invest 75:754–761, 1985Google Scholar
- 25.Hanson RG, Peters MG, Hoofnagle JH. Effect of immunosuppressive therapy with prednisolone on B and T lymphocyte function in patients with chronic type B hepatitis. Hepatology 6:173–179, 1986Google Scholar