Circulating activated B cells in primary biliary cirrhosis
- 30 Downloads
- 21 Citations
Abstract
Since patients with primary biliary cirrhosis (PBC) have evidence of abnormal function of the humoral immune system, we determined if B cells from patients with this disease show evidence of activation and can be stimulated by polyclonal activators. Using a reverse hemolytic plaque assay, it was found that patients with PBC had a significant increase in the number of circulating immunoglobulin-secreting cells, compared to normal controls and patients with chronic type B hepatitis virus (HBV) infection. However, the total number of activated cells was less than 1% of the total circulating B-cell population. Furthermore, we were unable to detect an increase in the expression of transferrin receptors, a membrane receptor associated with B-cell activation, in the majority of B cells in patients with PBC. In other studies, immunoglobulin production by lymphocytes from patients with PBC, when stimulated with the polyclonal activators pokeweed mitogen and Epstein-Barr virus (EBV), was reduced. This hyporesponsiveness was not due to a decrease in the number of B cells, as determined by staining with the monoclonal antibody anti-Leu 12. Furthermore, the decreased response of B cells to polyclonal activation in PBC patients was not due increased suppressor T-cell function, since EBV-stimulated cultures of lymphocytes from patients with PBC demonstrated diminished suppression of immunoglobulin-secreting cells after 14 days of culture compared to controls. These findings suggest that the humoral abnormalities in PBC are due to the activation of a small subpopulation of B cells rather than to generalized B-cell hyperactivity.
Key words
Primary biliary cirrhosis B cell activationPreview
Unable to display preview. Download preview PDF.
References
- 1.James SP, Hoofnagle JH, Strober W, Jones EA: Primary biliary cirrhosis: A model autoimmune disease. Ann Intern Med 99:500–512, 1983PubMedGoogle Scholar
- 2.James SP, Elson CO, Jones EA, Strober W: Abnormal regulation of immunoglobulin synthesis in primary biliary cirrhosis. Gastroenterology 79:242–254, 1980PubMedGoogle Scholar
- 3.James SP, Elson CO, Waggoner JG, Jones EA, Strober W: Deficiency of the autologous mixed lymphocyte reaction in patients with primary biliary cirrhosis. J Clin Invest 66:1305–1310, 1980PubMedGoogle Scholar
- 4.MacSween RNM, Horne CHW, Mofat AJ, Hughes HM: Serum protein levels in primary biliary cirrhosis. J Clin Pathol 25:789–792, 1972PubMedGoogle Scholar
- 5.Walker JG, Doniach D, Roitt IM, Sherlock S: Serological tests in the diagnosis of primary biliary cirrhosis. Lancet 1:827–831, 1965Google Scholar
- 6.Jones EA, Frank MM, Jaffe CJ, Vierling JM: Primary biliary cirrhosis and the complement system. Ann Intern Med 90:72–84, 1979PubMedGoogle Scholar
- 7.Steinberg AD, Raveché ES, Laskin CA, Smith HR, Santoro T, Miller ML, Plotz PH: Systemic lupus erythematosus. Insights from animal models. Ann Intern Med 100:714–727, 1984PubMedGoogle Scholar
- 8.Scheuer PJ: Liver Biopsy Interpretation, 3rd ed. London, Baillière Tindall, 1980, pp 36–59Google Scholar
- 9.Neckers LM, Yenokida G, James SP: The role of the transferrin receptor in human B lymphocyte activation. J Immunol 188:2437–2445, 1984Google Scholar
- 10.Kehrl J, Muraguchi A, Fauci AS: Differential expression of cell activation markers after stimulation of resting human B lymphocytes. J Immunol 132:2857–2861, 1984PubMedGoogle Scholar
- 11.Kirchner H, Tosato G, Blaese RM, Broder S, Magrath IT: Polyclonal immunoglobulin secretion by human B lymphocytes exposed to Epstein-Barr virusin vitro. J Immunol 122:1310–1313, 1979PubMedGoogle Scholar
- 12.Blaese RM, Grayson J, Steinberg AD: Increased immunoglobulin-secreting cells in the blood of patients with active systemic lupus erythematosus. Am J Med 79:345–350, 1980Google Scholar
- 13.Kaplan MM, Rocklin RE: In vitro regulation of antimitochondrial antibody synthesis in primary biliary cirrhosis. Hepatology 4-1032, 1984 (abstr)Google Scholar
- 14.Lemm G, Salzer K, Warnatz H: Studies on immunoregulatory mechanisms in acute and chronic hepatitis B. Clin Exp Immunol 52:250–258, 1983PubMedGoogle Scholar
- 15.Yarchoan R, Tosato G, Blaese RM, Nelson DL: Limiting dilution analysis of Epstein-Barr virus-induced immunoglobulin production by human B cells. J Exp Med 157:1–14, 1981Google Scholar
- 16.Martinez-Maza O, Britton S: Frequencies of the separate human B cell subsets activatable to Ig secretion by Epstein-Barr virus and pokeweed mitogen. J Exp Med 157:1808–1814, 1983PubMedGoogle Scholar
- 17.Fox RA, Dudley FJ, Sherlock S: The primary immune response to haemocyanin in patients with primary biliary cirrhosis. Clin Exp Immunol 14:473–480, 1973PubMedGoogle Scholar
- 18.Thomas HC, Holden R, Verrier Jones J, Peacock DB: Immune response to OX174 in man. 5. Primary and secondary antibody production in primary biliary cirrhosis. Gut 17:844–848, 1976PubMedGoogle Scholar
- 19.Zetterman RK, Woltjen JA: Suppressor cell activity in primary biliary cirrhosis. Digest Dis Sci 25:104–107, 1980PubMedGoogle Scholar
- 20.Alexander GJ, Nouri-Aria KT, Eddleston AL, Williams R: Contrasting relations between suppressor cell function and suppressor cell number in chronic liver disease. Lancet 1:1291–1293, 1983PubMedGoogle Scholar
- 21.Tosato G, Magrath IT, Blaese RM: T cell mediated immunoregulation of Epstein-Barr (EBV) virus-induced B lymphocyte activation in EBV-seropositive and EBV-seronegative individuals. J Immunol 128:575–579, 1982PubMedGoogle Scholar
- 22.Tosato G, Steinberg AD, Blaese RM: Defective EBV-specific suppressor T cell function in rheumatoid arthritis. N Engl J Med 305:1238–1243, 1981PubMedGoogle Scholar
- 23.Tsokos GC, Magrath IT, Balow JE: Epstein-Barr virus induces normal B cell responses but defective suppressor T cell responses in patients with lupus erythematosus. J Immunol 131:1797–1801, 1983PubMedGoogle Scholar
- 24.Ahmed A, Scher I, Sharrow SO, Smith AH, Paul WE, Sachs DH, Sell KW: B lymphocyte heterogeneity: Development of an alloantiserum which distinguishes B lymphocyte differentiation alloantigens. J Exp Med 145:101–110, 1977PubMedGoogle Scholar
- 25.Steinberg EB, Santoro TJ, Chused TM, Smathers SA, Steinberg AD: Studies of congenic MRL-1pr/1pr.xid mice. J Immunol 131:2789–2795, 1983PubMedGoogle Scholar
- 26.Miller KB, Sepersky RA, Brown KM, Goldberg MJ, Kaplan MM: Genetic abnormalities of immunoregulation in primary biliary cirrhosis. Am J Med 75:75–80, 1983Google Scholar
- 27.Galbraith RM, Smith M, Mackenzie RM, Tee DE, Doniach D, Williams R: High prevalence of seroimmunologic abnormalities in relatives of patients with active chronic hepatitis or primary biliary cirrhosis. N Engl J Med 290:63–69, 1974PubMedGoogle Scholar
- 28.Salaspuro MP, Laitinen OI, Lehtola J, Makkonen H, Räsänen JA, Sipponen P. Immunological parameters, viral antibodies, and biochemical and histological findings in relatives of patients with chronic active hepatitis and primary biliary cirrhosis. Scand J Gastroenterol 11:313–320, 1976PubMedGoogle Scholar
- 29.Jaup BH, Zettergren LSW: Familial occurrence of primary biliary cirrhosis associated with hypergammaglobulinemia in descendants: A family study. Gastroenterology 78:549–555, 1980PubMedGoogle Scholar