Abstract
Precursor frequencies for anti-DNA-secreting B cells were estimated in six healthy donors and 18 SLE patients with active and inactive disease. Precursors for IgG anti-dsDNA-secreting B cells were exclusively detected in SLE patients (73% of active patients and one inactive patient, 0.01-0.99% of IgG-producing B cells). These frequencies were in the same order of magnitude as frequencies of precursors for IgG anti-tetanus toxoid, which were detectable in three healthy volunteers after booster vaccination (0.07-0.8% of IgG-producing B cells), but not before (< 0.01%). Precursors for IgG anti-ss-DNA secreting B cells were observed in 33% of healthy donors and in 78% of SLE patients (0.01-0.32% of IgG-producing B cells). Only patient-derived IgG anti-DNA clones cross-reacted with (33%) or were monoreactive to dsDNA (12%). Precursors for IgM anti-DNA-secreting B cells were observed in healthy donors and SLE patients in comparable frequencies and with similar reactivities with ssDNA and dsDNA. Segregation analyses and sorting experiments showed that > 94% of clones secreting IgG anti-DNA were derived from in vivo sIgG+ B cells. sIgM+ B cells were induced to switch in vitro; however, only twice were cultures containing IgM and IgG anti-DNA antibodies observed under clonal conditions. In conclusion, our results indicate that precursor B cells for IgG anti-dsDNA in SLE patients are similarly selected and expanded as are precursor B cells specific for foreign antigens such as tetanus toxoid.
Full text
PDF







Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Avrameas S., Guilbert B., Mahana W., Matsiota P., Ternynck T. Recognition of self and non-self constituents by polyspecific autoreceptors. Int Rev Immunol. 1988 Mar;3(1-2):1–15. doi: 10.3109/08830188809051179. [DOI] [PubMed] [Google Scholar]
- Blaese R. M., Grayson J., Steinberg A. D. Increased immunoglobulin-secreting cells in the blood of patients with active systemic lupus erythematosus. Am J Med. 1980 Sep;69(3):345–350. doi: 10.1016/0002-9343(80)90003-0. [DOI] [PubMed] [Google Scholar]
- Casali P., Burastero S. E., Nakamura M., Inghirami G., Notkins A. L. Human lymphocytes making rheumatoid factor and antibody to ssDNA belong to Leu-1+ B-cell subset. Science. 1987 Apr 3;236(4797):77–81. doi: 10.1126/science.3105056. [DOI] [PubMed] [Google Scholar]
- Dilosa R. M., Maeda K., Masuda A., Szakal A. K., Tew J. G. Germinal center B cells and antibody production in the bone marrow. J Immunol. 1991 Jun 15;146(12):4071–4077. [PubMed] [Google Scholar]
- Dziarski R. Autoimmunity: polyclonal activation or antigen induction? Immunol Today. 1988 Nov;9(11):340–342. doi: 10.1016/0167-5699(88)91333-3. [DOI] [PubMed] [Google Scholar]
- Fish F., Ziff M. A sensitive solid phase microradioimmunoassay for anti-double stranded DNA antibodies. Arthritis Rheum. 1981 Mar;24(3):534–543. doi: 10.1002/art.1780240314. [DOI] [PubMed] [Google Scholar]
- Klinman D. M., Eisenberg R. A., Steinberg A. D. Development of the autoimmune B cell repertoire in MRL-lpr/lpr mice. J Immunol. 1990 Jan 15;144(2):506–511. [PubMed] [Google Scholar]
- Liu Y. J., Johnson G. D., Gordon J., MacLennan I. C. Germinal centres in T-cell-dependent antibody responses. Immunol Today. 1992 Jan;13(1):17–21. doi: 10.1016/0167-5699(92)90199-H. [DOI] [PubMed] [Google Scholar]
- Lydyard P. M., Quartey-Papafio R., Bröker B., Mackenzie L., Jouquan J., Blaschek M. A., Steele J., Petrou M., Collins P., Isenberg D. The antibody repertoire of early human B cells. I. High frequency of autoreactivity and polyreactivity. Scand J Immunol. 1990 Jan;31(1):33–43. doi: 10.1111/j.1365-3083.1990.tb02740.x. [DOI] [PubMed] [Google Scholar]
- Nakamura M., Burastero S. E., Ueki Y., Larrick J. W., Notkins A. L., Casali P. Probing the normal and autoimmune B cell repertoire with Epstein-Barr virus. Frequency of B cells producing monoreactive high affinity autoantibodies in patients with Hashimoto's disease and systemic lupus erythematosus. J Immunol. 1988 Dec 15;141(12):4165–4172. [PubMed] [Google Scholar]
- Pearson L., Lightfoot R. W., Jr Correlation of DNA-anti-DNA association rates with clinical activity in systemic lupus erythematosus (SLE). J Immunol. 1981 Jan;126(1):16–19. [PubMed] [Google Scholar]
- Rudolphi U., Hohlbaum A., Lang B., Peter H. H., Melchers I. The B cell repertoire of patients with rheumatoid arthritis. Frequencies and specificities of peripheral blood B cells reacting with human IgG, human collagens, a mycobacterial heat shock protein and other antigens. Clin Exp Immunol. 1993 Jun;92(3):404–411. doi: 10.1111/j.1365-2249.1993.tb03412.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Röther E., Lang B., Coldewey R., Hartung K., Peter H. H. Complement split product C3d as an indicator of disease activity in systemic lupus erythematosus. Clin Rheumatol. 1993 Mar;12(1):31–35. doi: 10.1007/BF02231555. [DOI] [PubMed] [Google Scholar]
- Shlomchik M., Mascelli M., Shan H., Radic M. Z., Pisetsky D., Marshak-Rothstein A., Weigert M. Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation. J Exp Med. 1990 Jan 1;171(1):265–292. doi: 10.1084/jem.171.1.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Suzuki N., Sakane T. Induction of excessive B cell proliferation and differentiation by an in vitro stimulus in culture in human systemic lupus erythematosus. J Clin Invest. 1989 Mar;83(3):937–944. doi: 10.1172/JCI113979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taki S., Schmitt M., Tarlinton D., Förster I., Rajewsky K. T cell-dependent antibody production by Ly-1 B cells. Ann N Y Acad Sci. 1992 May 4;651:328–335. doi: 10.1111/j.1749-6632.1992.tb24632.x. [DOI] [PubMed] [Google Scholar]
- Tan E. M. Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv Immunol. 1989;44:93–151. doi: 10.1016/s0065-2776(08)60641-0. [DOI] [PubMed] [Google Scholar]
- Tan E. M., Cohen A. S., Fries J. F., Masi A. T., McShane D. J., Rothfield N. F., Schaller J. G., Talal N., Winchester R. J. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. doi: 10.1002/art.1780251101. [DOI] [PubMed] [Google Scholar]
- Taswell C. Limiting dilution assays for the determination of immunocompetent cell frequencies. I. Data analysis. J Immunol. 1981 Apr;126(4):1614–1619. [PubMed] [Google Scholar]
- Tillman D. M., Jou N. T., Hill R. J., Marion T. N. Both IgM and IgG anti-DNA antibodies are the products of clonally selective B cell stimulation in (NZB x NZW)F1 mice. J Exp Med. 1992 Sep 1;176(3):761–779. doi: 10.1084/jem.176.3.761. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wen L., Hanvanich M., Werner-Favre C., Brouwers N., Perrin L. H., Zubler R. H. Limiting dilution assay for human B cells based on their activation by mutant EL4 thymoma cells: total and antimalaria responder B cell frequencies. Eur J Immunol. 1987 Jun;17(6):887–892. doi: 10.1002/eji.1830170624. [DOI] [PubMed] [Google Scholar]
- Winfield J. B., Faiferman I., Koffler D. Avidity of anti-DNA antibodies in serum and IgG glomerular eluates from patients with systemic lupus erythematosus. Association of high avidity antinative DNA antibody with glomerulonephritis. J Clin Invest. 1977 Jan;59(1):90–96. doi: 10.1172/JCI108626. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Winkler T. H., Fehr H., Kalden J. R. Analysis of immunoglobulin variable region genes from human IgG anti-DNA hybridomas. Eur J Immunol. 1992 Jul;22(7):1719–1728. doi: 10.1002/eji.1830220709. [DOI] [PubMed] [Google Scholar]
- Zouali M., Fournié G. J., Thèze J. Quantitative clonal analysis of the B cell repertoire in human lupus. Cell Immunol. 1991 Mar;133(1):161–177. doi: 10.1016/0008-8749(91)90188-h. [DOI] [PubMed] [Google Scholar]
- van Es J. H., Gmelig Meyling F. H., van de Akker W. R., Aanstoot H., Derksen R. H., Logtenberg T. Somatic mutations in the variable regions of a human IgG anti-double-stranded DNA autoantibody suggest a role for antigen in the induction of systemic lupus erythematosus. J Exp Med. 1991 Feb 1;173(2):461–470. doi: 10.1084/jem.173.2.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
