Defective Immunoglobulin Secretion in Response to Pokeweed Mitogen in Sarcoidosis

Overview

Journal Clin Exp Immunol

Publisher Oxford University Press

Specialty Allergy & Immunology

Date 1982 Jul 1

PMID 6215196

Authors

E C Lawrence

B J Theodore

R B Teague

M S Gottlieb

Affiliations

Soon will be listed here.

Abstract

We studied in vitro immunoregulation of immunoglobulin (Ig) secretion in 21 patients with sarcoidosis. While peripheral blood mononuclear cells from normal individuals responded to pokeweed mitogen with a 10-fold or greater increment in Ig-secreting cells, cells from sarcoid patients failed to respond to pokeweed mitogen at any concentration employed (P less than 0.001, Student's t-test, two-tailed). More monocytes were found in sarcoid mononuclear cell preparations (44.8 +/- 2.0% vs 30.4 +/- 1.4% in normal donors, P less than 0.001), but removal of monocytes improved the response to pokeweed mitogen in only four patients. Mononuclear cells from seven of 19 patients suppressed Ig secretion in co-cultures with normal donor cells. Patients exhibiting excessive suppressor cell function were older, with longer standing and less clinically active disease than non-suppressing patients. Monocyte removal reversed the suppression in only four of the suppressor patients, but excessive suppressor monocyte function was later demonstrated in two sarcoid patients whose cells initially did not suppress Ig secretion when cultured with normal cells. While the immunological defects in sarcoidosis may be complex, heterogenous, and dynamic, these data suggest that suppressor monocytes, when present in sarcoidosis, may have developed secondarily.

References

Waldmann T, Durm M, Broder S, Blackman M, Blaese R, Strober W . Role of suppressor T cells in pathogenesis of common variable hypogammaglobulinaemia. Lancet. 1974; 2(7881):609-13. DOI: 10.1016/s0140-6736(74)91940-0. View

MITCHELL D, Scadding J . Sarcoidosis. Am Rev Respir Dis. 1974; 110(6):774-802. DOI: 10.1164/arrd.1974.110.6P1.774. View

Broder S, Humphrey R, Durm M, Blackman M, Meade B, Goldman C . Impaired synthesis of polyclonal (non-paraprotein) immunoglobulins by circulating lymphocytes from patients with multiple myeloma Role of suppressor cells. N Engl J Med. 1975; 293(18):887-92. DOI: 10.1056/NEJM197510302931801. View

Nelson D, Bundy B, Pitchon H, Blaese R, Strober W . The effector cells in human peripheral blood mediating mitogen-induced cellular cytotoxicity and antibody-dependent cellular cytotoxicity. J Immunol. 1976; 117(5 Pt 1):1472-81. View

Laughter A, TWOMEY J . Suppression of lymphoproliferation by high concentrations of normal human mononuclear leukocytes. J Immunol. 1977; 119(1):173-9. View

Katz P, Fauci A . Inhibition of polyclonal B-cell activation by suppressor monocytes in patients with sarcoidosis. Clin Exp Immunol. 1978; 32(3):554-62. PMC: 1541315. View

Lawrence E, Blaese R, Martin R, Stevens P . Immunoglobulin secreting cells in normal human bronchial lavage fluids. J Clin Invest. 1978; 62(4):832-5. PMC: 371835. DOI: 10.1172/JCI109195. View

Katz P, Fauci A . The effects of corticosteroids on immunoregulation in sarcoidosis. Cell Immunol. 1979; 42(2):308-18. DOI: 10.1016/0008-8749(79)90196-5. View

Goodwin J, DeHoratius R, Israel H, Peake G, Messner R . Suppressor cell function in sarcoidosis. Ann Intern Med. 1979; 90(2):169-73. DOI: 10.7326/0003-4819-90-2-169. View

10.

Rosenberg S, Lipsky P . Monocyte dependence of pokeweed mitogen-induced differentiation of immunoglobulin-secreting cells from human peripheral blood mononuclear cells. J Immunol. 1979; 122(3):926-31. View

11.

Kirchner H, Tosato G, Blaese R, Broder S, Magrath I . Polyclonal immunoglobulin secretion by human B lymphocytes exposed to Epstein-Barr virus in vitro. J Immunol. 1979; 122(4):1310-3. View

12.

Lawrence E, Martin R, Blaese R, Teague R, Awe R, Wilson R . Increased bronchoalveolar IgG-secreting cells in interstitial lung diseases. N Engl J Med. 1980; 302(21):1186-8. DOI: 10.1056/NEJM198005223022106. View

13.

Gmelig-Meyling F, Waldmann T . Human B cell activation in vitro: augmentation and suppression by monocytes of the immunoglobulin production induced by various B cell stimulants. J Immunol. 1981; 126(2):529-37. View

14.

Line B, Hunninghake G, Keogh B, Jones A, Johnston G, Crystal R . Gallium-67 scanning to stage the alveolitis of sarcoidosis: correlation with clinical studies, pulmonary function studies, and bronchoalveolar lavage. Am Rev Respir Dis. 1981; 123(4 Pt 1):440-6. DOI: 10.1164/arrd.1981.123.4.440. View