Abstract
Epstein-Barr (EBV)-immortalized B cell clones were established from CD5+ and CD5- cord blood B cells separated by flow cytometry. We have previously shown that IgM from many of the clones was polyreactive, exhibiting reactivity with a number of autoantigens. In this study, IgM produced by the clones was analysed by MoAb for the expression of cross-reactive idiotypes (CRI) associated with rheumatoid factor paraproteins and from defined VH and V kappa subgroups of immunoglobulin heavy and light chains. IgM produced by clones established from CD5+ and CD5- B cells expressed the VH I associated idiotope G8. Furthermore, IgM produced by both sets of clones exhibited a similar frequency of VH III heavy chain subgroup expression, as determined by reactivity with staphylococcal protein A (SpA) and VH III-associated CRI expression (B6 and/or D12). In contrast, expression of the V kappa III-associated 17.109 CRI was significantly higher in IgM antibodies produced by clones established from CD5+ compared with the CD5- clones (32 versus 5%: P less than 0.05). Analysis of the VH and VL subgroup expression by IgM produced by the CD5+ and CD5- cord blood clones, and their autoantigen reactivity profile did not reveal restriction or selection within CD5+ and CD5- populations. However, our data suggest that differences may exist in the expression of certain germ-line genes between CD5+ and CD5- cord blood B cells and might indicate an expansion of CD5+ B cells within the fetal environment.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Andrade L., Freitas A. A., Huetz F., Poncet P., Coutinho A. Immunoglobulin VH gene expression in Ly-1+ and conventional B lymphocytes. Eur J Immunol. 1989 Jun;19(6):1117–1122. doi: 10.1002/eji.1830190623. [DOI] [PubMed] [Google Scholar]
- Bröker B. M., Klajman A., Youinou P., Jouquan J., Worman C. P., Murphy J., Mackenzie L., Quartey-Papafio R., Blaschek M., Collins P. Chronic lymphocytic leukemic (CLL) cells secrete multispecific autoantibodies. J Autoimmun. 1988 Oct;1(5):469–481. doi: 10.1016/0896-8411(88)90068-6. [DOI] [PubMed] [Google Scholar]
- Carson D. A., Fong S. A common idiotope on human rheumatoid factors identified by a hybridoma antibody. Mol Immunol. 1983 Oct;20(10):1081–1087. doi: 10.1016/0161-5890(83)90116-5. [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]
- Crowley J. J., Goldfien R. D., Schrohenloher R. E., Spiegelberg H. L., Silverman G. J., Mageed R. A., Jefferis R., Koopman W. J., Carson D. A., Fong S. Incidence of three cross-reactive idiotypes on human rheumatoid factor paraproteins. J Immunol. 1988 May 15;140(10):3411–3418. [PubMed] [Google Scholar]
- Crowley J. J., Mageed R. A., Silverman G. J., Chen P. P., Kozin F., Erger R. A., Jefferis R., Carson D. A. The incidence of a new human cross-reactive idiotype linked to subgroup VHIII heavy chains. Mol Immunol. 1990 Jan;27(1):87–94. doi: 10.1016/0161-5890(90)90063-6. [DOI] [PubMed] [Google Scholar]
- Förster I., Gu H., Rajewsky K. Germline antibody V regions as determinants of clonal persistence and malignant growth in the B cell compartment. EMBO J. 1988 Dec 1;7(12):3693–3703. doi: 10.1002/j.1460-2075.1988.tb03251.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hardy R. R., Hayakawa K. Development and physiology of Ly-1 B and its human homolog, Leu-1 B. Immunol Rev. 1986 Oct;93:53–79. doi: 10.1111/j.1600-065x.1986.tb01502.x. [DOI] [PubMed] [Google Scholar]
- Hardy R. R., Hayakawa K., Shimizu M., Yamasaki K., Kishimoto T. Rheumatoid factor secretion from human Leu-1+ B cells. Science. 1987 Apr 3;236(4797):81–83. doi: 10.1126/science.3105057. [DOI] [PubMed] [Google Scholar]
- Kipps T. J., Robbins B. A., Carson D. A. Uniform high frequency expression of autoantibody-associated crossreactive idiotypes in the primary B cell follicles of human fetal spleen. J Exp Med. 1990 Jan 1;171(1):189–196. doi: 10.1084/jem.171.1.189. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kipps T. J., Tomhave E., Chen P. P., Carson D. A. Autoantibody-associated kappa light chain variable region gene expressed in chronic lymphocytic leukemia with little or no somatic mutation. Implications for etiology and immunotherapy. J Exp Med. 1988 Mar 1;167(3):840–852. doi: 10.1084/jem.167.3.840. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kipps T. J., Tomhave E., Pratt L. F., Duffy S., Chen P. P., Carson D. A. Developmentally restricted immunoglobulin heavy chain variable region gene expressed at high frequency in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5913–5917. doi: 10.1073/pnas.86.15.5913. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee K. H., Matsuda F., Kinashi T., Kodaira M., Honjo T. A novel family of variable region genes of the human immunoglobulin heavy chain. J Mol Biol. 1987 Jun 20;195(4):761–768. doi: 10.1016/0022-2836(87)90482-7. [DOI] [PubMed] [Google Scholar]
- Ling N. R., Bishop S., Jefferis Use of antibody-coated red cells for the sensitive detection of antigen and in rosette tests for cells bearing surface immunoglobulins. J Immunol Methods. 1977;15(3):279–289. doi: 10.1016/0022-1759(77)90065-5. [DOI] [PubMed] [Google Scholar]
- Lydyard P. M., Quartey-Papafio R. P., Bröker B. M., MacKenzie L., Hay F. C., Youinou P. Y., Jefferis R., Mageed R. A. The antibody repertoire of early human B cells. III. Expression of cross-reactive idiotopes characteristic of certain rheumatoid factors and identifying V kappa III, VHI, and VHIII gene family products. Scand J Immunol. 1990 Dec;32(6):709–716. doi: 10.1111/j.1365-3083.1990.tb03214.x. [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]
- Mackenzie L. E., Youinou P. Y., Hicks R., Yuksel B., Mageed R. A., Lydyard P. M. Auto- and polyreactivity of IgM from CD5+ and CD5- cord blood B cells. Scand J Immunol. 1991 Mar;33(3):329–335. doi: 10.1111/j.1365-3083.1991.tb01778.x. [DOI] [PubMed] [Google Scholar]
- Mageed R. A., Dearlove M., Goodall D. M., Jefferis R. Immunogenic and antigenic epitopes of immunoglobulins. XVII--Monoclonal antibodies reactive with common and restricted idiotopes to the heavy chain of human rheumatoid factors. Rheumatol Int. 1986;6(4):179–183. doi: 10.1007/BF00541285. [DOI] [PubMed] [Google Scholar]
- Mageed R. A., Goodall D. M., Jefferis R. A highly conserved conformational idiotope on human IgM rheumatoid factor paraproteins of the Wa cross-reactive idiotype family defined by a monoclonal antibody. Rheumatol Int. 1990;10(2):57–63. doi: 10.1007/BF02274784. [DOI] [PubMed] [Google Scholar]
- Mageed R. A., MacKenzie L. E., Stevenson F. K., Yuksel B., Shokri F., Maziak B. R., Jefferis R., Lydyard P. M. Selective expression of a VHIV subfamily of immunoglobulin genes in human CD5+ B lymphocytes from cord blood. J Exp Med. 1991 Jul 1;174(1):109–113. doi: 10.1084/jem.174.1.109. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mageed R. A., Walker M. R., Jefferis R. Restricted light chain subgroup expression on human rheumatoid factor paraproteins determined by monoclonal antibodies. Immunology. 1986 Nov;59(3):473–478. [PMC free article] [PubMed] [Google Scholar]
- Nakamura M., Burastero S. E., Notkins A. L., Casal P. Human monoclonal rheumatoid factor-like antibodies from CD5 (Leu-1)+ B cells are polyreactive. J Immunol. 1988 Jun 15;140(12):4180–4186. [PubMed] [Google Scholar]
- Radoux V., Chen P. P., Sorge J. A., Carson D. A. A conserved human germline V kappa gene directly encodes rheumatoid factor light chains. J Exp Med. 1986 Dec 1;164(6):2119–2124. doi: 10.1084/jem.164.6.2119. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sasso E. H., Silverman G. J., Mannik M. Human IgM molecules that bind staphylococcal protein A contain VHIII H chains. J Immunol. 1989 Apr 15;142(8):2778–2783. [PubMed] [Google Scholar]
- Shokri F., Mageed R. A., Maziak B. R., Jefferis R. Expression of VHIII-associated cross-reactive idiotype on human B lymphocytes. Association with staphylococcal protein A binding and Staphylococcus aureus Cowan I stimulation. J Immunol. 1991 Feb 1;146(3):936–940. [PubMed] [Google Scholar]
- Shokri F., Mageed R. A., Tunn E., Bacon P. A., Jefferis R. Qualitative and quantitative expression of VHI associated cross reactive idiotopes within IgM rheumatoid factor from patients with early synovitis. Ann Rheum Dis. 1990 Mar;49(3):150–154. doi: 10.1136/ard.49.3.150. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Silverman G. J., Goñi F., Fernandez J., Chen P. P., Frangione B., Carson D. A. Distinct patterns of heavy chain variable region subgroup use by human monoclonal autoantibodies of different specificity. J Exp Med. 1988 Dec 1;168(6):2361–2366. doi: 10.1084/jem.168.6.2361. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Souroujon M. C., Rubinstein D. B., Schwartz R. S., Barrett K. J. Polymorphisms in human H chain V region genes from the VHIII gene family. J Immunol. 1989 Jul 15;143(2):706–711. [PubMed] [Google Scholar]
- Sthoeger Z. M., Wakai M., Tse D. B., Vinciguerra V. P., Allen S. L., Budman D. R., Lichtman S. M., Schulman P., Weiselberg L. R., Chiorazzi N. Production of autoantibodies by CD5-expressing B lymphocytes from patients with chronic lymphocytic leukemia. J Exp Med. 1989 Jan 1;169(1):255–268. doi: 10.1084/jem.169.1.255. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Youinou P., Le Goff P., Colaco C. B., Thivolet J., Tater D., Viac J., Shipley M. Antikeratin antibodies in serum and synovial fluid show specificity for rheumatoid arthritis in a study of connective tissue diseases. Ann Rheum Dis. 1985 Jul;44(7):450–454. doi: 10.1136/ard.44.7.450. [DOI] [PMC free article] [PubMed] [Google Scholar]