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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1975 Dec;56(6):1378–1385. doi: 10.1172/JCI108218

Identification of DNA-binding lymphocytes in patients with systemic lupus erythematosus.

A D Bankhurst, R C Williams Jr
PMCID: PMC333115  PMID: 1081549

Abstract

Antigen-ginding lymphocytes capable of binding native DNA (DNA-ABC) were identified in the peripheral blood of normal controls and patients with systemic lupus erythematosus (SLE) by autoradiography with 125I-nDNA. 12 patients with active SLE had 404 +/- 273 (mean +/- SD) DNA-ABC/105 lymphocytes, while 7 inactive SLE patients and 13 normals had 120 +/- 48 and 48 +/- 36, respectively. All three groups were significantly different from one another (p less than 0.01). No significant correlation was detected between the quantity of anti-native DNA (nDNA) antibody and number of DNA-ABC; however, most patients with large amounts of anti-nDNA antibody had both active disease and large numbers of DNA-ABC. Numbers of DNA-ABC and lymphocytes with surface immunoglobulin (Ig) did not change significantly after an 18-h incubation at 37degreeC. After depletion of B-lymphocytes by passage over bead columns coated with a complex of IgG and anti-IgG, the great majority of DNA-ABC were removed in both normal subjects and SLE patients. Labeling lymphocytes sequentially with 125I-nDNA, followed by an indirect fluorescence technique for identification of surface Ig, indicated that the great mahority of radiolabeled cells had surface Ig by fluorescence microscopy in four normals (average 93%) and five patients with active SLF (average 82%). The predominance of nDNA-sensitive B-lymphocytes in the peripheral blood of both normals and SLE patients is consistent with the concept that the induction of the anti-nDNA antibody response is due to the stimulation of preexisting nDNA-specific B lymphocytes by mechanisms other than those necessarily involving participation of nDNA-specific T lymphocytes.

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Selected References

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  1. Ada G. L. Antigen binding cells in tolerance and immunity. Transplant Rev. 1970;5:105–129. doi: 10.1111/j.1600-065x.1970.tb00358.x. [DOI] [PubMed] [Google Scholar]
  2. Ada G. L., Byrt P. Specific inactivation of antigen-reactive cells with 125I-labelled antigen. Nature. 1969 Jun 28;222(5200):1291–1292. doi: 10.1038/2221291a0. [DOI] [PubMed] [Google Scholar]
  3. Allison A. C. Unresponsiveness to self antigens. Lancet. 1971 Dec 25;2(7739):1401–1403. doi: 10.1016/s0140-6736(71)90673-8. [DOI] [PubMed] [Google Scholar]
  4. Arana R., Seligmann M. Antibodies to native and denatured deoxyribonucleic acid in systemic lupus erythematosus. J Clin Invest. 1967 Nov;46(11):1867–1882. doi: 10.1172/JCI105677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bankhurst A. D., Torrigiani G., Allison A. C. Lymphocytes binding human thyroglobulin in healthy people and its relevance to tolerance for autoantigens. Lancet. 1973 Feb 3;1(7797):226–230. doi: 10.1016/s0140-6736(73)90066-4. [DOI] [PubMed] [Google Scholar]
  6. Basten A., Miller J. F., Sprent J., Pye J. A receptor for antibody on B lymphocytes. I. Method of detection and functional significance. J Exp Med. 1972 Mar 1;135(3):610–626. doi: 10.1084/jem.135.3.610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bobrove A. M., Strober S., Herzenberg L. A., DePamphilis J. D. Identification and quantitation of thymus-derived lymphocytes in human peripheral blood. J Immunol. 1974 Feb;112(2):520–527. [PubMed] [Google Scholar]
  8. Byrt P., Ada G. L. An in vitro reaction between labelled flagellin or haemocyanin and lymphocyte-like cells from normal animals. Immunology. 1969 Oct;17(4):503–516. [PMC free article] [PubMed] [Google Scholar]
  9. Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
  10. Cohen A. S., Canoso J. J. Criteria for the classification of systemic lupus erythematosus--status 1972. Arthritis Rheum. 1972 Sep-Oct;15(5):540–543. doi: 10.1002/art.1780150512. [DOI] [PubMed] [Google Scholar]
  11. Cohn Z. A. The structure and function of monocytes and macrophages. Adv Immunol. 1968;9:163–214. doi: 10.1016/s0065-2776(08)60443-5. [DOI] [PubMed] [Google Scholar]
  12. Commerford S. L. Iodination of nucleic acids in vitro. Biochemistry. 1971 May 25;10(11):1993–2000. doi: 10.1021/bi00787a005. [DOI] [PubMed] [Google Scholar]
  13. Cone R. E., Marchalonis J. J., Rolley R. T. Lymphocyte membrane dynamics. Metabolic release of cell surface proteins. J Exp Med. 1971 Dec 1;134(6):1373–1384. doi: 10.1084/jem.134.6.1373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Davie J. M., Paul W. E. Receptors on immunocompetent cells. I. Receptor specificity of cells participating in a cellular immune response. Cell Immunol. 1970 Oct;1(4):404–418. doi: 10.1016/0008-8749(70)90017-1. [DOI] [PubMed] [Google Scholar]
  15. Davie J. M., Rosenthal A. S., Paul W. E. Receptors on immunocompetent cells. 3. Specificity and nature of receptors on dinitrophenylated guinea pig albumin- 125 I-binding cells of immunized guinea pigs. J Exp Med. 1971 Aug 1;134(2):517–531. doi: 10.1084/jem.134.2.517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Dwyer J. M., Warner N. L., Mackay I. R. Specificity and nature of the antigen-combining sites on fetal and mature thymus lymphocytes. J Immunol. 1972 May;108(5):1439–1446. [PubMed] [Google Scholar]
  17. Ginsberg B., Keiser H. A Millipore filter assay for antibodies to native DNA in sera of patients with systemic lupus erythematosus. Arthritis Rheum. 1973 Mar-Apr;16(2):199–207. doi: 10.1002/art.1780160210. [DOI] [PubMed] [Google Scholar]
  18. HOLMAN H. R., KUNKEL H. G. Affinity between the lupus erythematosus serum factor and cell nuclei and nucleoprotein. Science. 1957 Jul 26;126(3265):162–163. doi: 10.1126/science.126.3265.162. [DOI] [PubMed] [Google Scholar]
  19. HOLMAN H., DEICHER H. R. The reaction of the lupus erythematosus (L.E.) cell factor with deoxyribonucleoprotein of the cell nucleus. J Clin Invest. 1959 Nov;38:2059–2072. doi: 10.1172/JCI103984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Harbeck R. J., Bardana E. J., Kohler P. F., Carr R. I. DNA:anti-DNA complexes: their detection in systemic lupus erythematosus sera. J Clin Invest. 1973 Apr;52(4):789–795. doi: 10.1172/JCI107242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hämmerling G. J., McDevitt H. O. Antigen binding T and B lymphocytes. I. Differences in cellular specificity and influence of metabolic activity on interaction of antigen with T and B cells. J Immunol. 1974 May;112(5):1726–1733. [PubMed] [Google Scholar]
  22. Koffler D., Agnello V., Thoburn R., Kunkel H. G. Systemic lupus erythematosus: prototype of immune complex nephritis in man. J Exp Med. 1971 Sep 1;134(3 Pt 2):169s–179s. [PubMed] [Google Scholar]
  23. Koffler D., Agnello V., Winchester R., Kunkel H. G. The occurrence of single-stranded DNA in the serum of patients with systemic lupus erythematosus and other diseases. J Clin Invest. 1973 Jan;52(1):198–204. doi: 10.1172/JCI107165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Koffler D., Carr R. I., Agnello V., Fiezi T., Kunkel H. G. Antibodies to polynucleotides: distribution in human serums. Science. 1969 Dec 26;166(3913):1648–1649. doi: 10.1126/science.166.3913.1648. [DOI] [PubMed] [Google Scholar]
  25. Koffler D., Schur P. H., Kunkel H. G. Immunological studies concerning the nephritis of systemic lupus erythematosus. J Exp Med. 1967 Oct 1;126(4):607–624. doi: 10.1084/jem.126.4.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Krishnan C., Kaplan M. H. Immunopathologic studies of systemic lupus erythematosus. II. Antinuclear reaction of gamma-globulin eluted from homogenates and isolated glomeruli of kidneys from patients with lupus nephritis. J Clin Invest. 1967 Apr;46(4):569–579. doi: 10.1172/JCI105558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  28. Lies R. B., Messner R. P., Williams R. C., Jr Relative T-cell specificity of lymphocytotoxins from patients with systemic lupus erythematosus. Arthritis Rheum. 1973 May-Jun;16(3):369–375. doi: 10.1002/art.1780160312. [DOI] [PubMed] [Google Scholar]
  29. ROBBINS W. C., HOLMAN H. R., DEICHER H., KUNKEL H. G. Complement fixation with cell nuclei and DNA in lupus erythematosus. Proc Soc Exp Biol Med. 1957 Dec;96(3):575–579. doi: 10.3181/00379727-96-23545. [DOI] [PubMed] [Google Scholar]
  30. Roberts I. M., Whittingham S., Mackay I. R. Tolerance to an autoantigen-thyroglobulin. Antigen-binding lymphocytes in thymus and blood in health and autoimmune disease. Lancet. 1973 Oct 27;2(7835):936–940. doi: 10.1016/s0140-6736(73)92598-1. [DOI] [PubMed] [Google Scholar]
  31. SELIGMANN M. Mise en évidence dans le sérum de malades atteints de lupus erythémateux disséminé d'une substance déterminant une réaction de précipitation avec l'acide désoxyribonucléique. C R Hebd Seances Acad Sci. 1957 Jul 8;245(2):243–245. [PubMed] [Google Scholar]
  32. STOLLAR D., LEVINE L., LEHRER H. I., VAN VUNAKIS H. The antigenic determinants of denatured DNA reactive with lupus erythematosus serum. Proc Natl Acad Sci U S A. 1962 May 15;48:874–880. doi: 10.1073/pnas.48.5.874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Schur P. H., Sandson J. Immunologic factors and clinical activity in systemic lupus erythematosus. N Engl J Med. 1968 Mar 7;278(10):533–538. doi: 10.1056/NEJM196803072781004. [DOI] [PubMed] [Google Scholar]
  34. Sjöquist J., Meloun B., Hjelm H. Protein A isolated from Staphylococcus aureus after digestion with lysostaphin. Eur J Biochem. 1972 Sep 25;29(3):572–578. doi: 10.1111/j.1432-1033.1972.tb02023.x. [DOI] [PubMed] [Google Scholar]
  35. Talal N., Steinberg A. D., Daley G. G. Inhibition of antigodies binding polyinosinic-polycytidylic acid in human and mouse lupus sera by viral and synthetic ribonucleic acids. J Clin Invest. 1971 Jun;50(6):1248–1252. doi: 10.1172/JCI106602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Tan E. M., Kunkel H. G. Characteristics of a soluble nuclear antigen precipitating with sera of patients with systemic lupus erythematosus. J Immunol. 1966 Mar;96(3):464–471. [PubMed] [Google Scholar]
  37. Tan E. M., Schur P. H., Carr R. I., Kunkel H. G. Deoxybonucleic acid (DNA) and antibodies to DNA in the serum of patients with systemic lupus erythematosus. J Clin Invest. 1966 Nov;45(11):1732–1740. doi: 10.1172/JCI105479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Uhr J. W. Passive sensitization of lymphocytes and macrophages by antigen-antibody complexes. Proc Natl Acad Sci U S A. 1965 Dec;54(6):1599–1606. doi: 10.1073/pnas.54.6.1599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Wernet P., Kunkel H. G. Antibodies to a specific surface antigen of T cells in human sera inhibiting mixed leukocyte culture reactions. J Exp Med. 1973 Oct 1;138(4):1021–1026. doi: 10.1084/jem.138.4.1021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Wigzell H., Sundqvist K. G., Yoshida T. O. Separation of cells according to surface antigens by the use of antibody-coated columns. Fractionation of cells carrying immunoglobulins and blood group antigen. Scand J Immunol. 1972;1(1):75–87. doi: 10.1111/j.1365-3083.1972.tb03737.x. [DOI] [PubMed] [Google Scholar]
  41. Wold R. T., Young F. E., Tan E. M., Farr R. S. Deoxyribonucleic acid antibody: a method to detect its primary interaction with deoxyribonucleic acid. Science. 1968 Aug 23;161(3843):806–807. doi: 10.1126/science.161.3843.806. [DOI] [PubMed] [Google Scholar]

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