Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1983 Dec 1;158(6):1993–2006. doi: 10.1084/jem.158.6.1993

Ultrastructural studies of human lymphoid cells. mu and J chain expression as a function of B cell differentiation

PMCID: PMC2187181  PMID: 6417260

Abstract

J chain expression was examined as a function of the stage in differentiation along the B cell axis in humans. Intracellular distribution of J and mu chains in leukemic HLA-DR+ null and pre-B cells, and in normal B cells stimulated with pokeweed mitogen (PWM) was determined by immunoelectron microscopy and radioimmunoassay (RIA). J chain was detected in leukemic null and pre-B cells on free and membrane-bound ribosomes in the cytoplasm, or on perinuclear cisternae. Mu chain was found on free ribosomes and ribosomal clusters in leukemic pre-B cells but was absent in the leukemic null cells. In pre-B cell lines, mu chain was seen within rough endoplasmic reticulum (RER) and the Golgi apparatus whereas J chain was not detected in these organelles. However, both mu and J chain were detected in RER and the Golgi apparatus of immature and mature plasma cells induced by PWM stimulation of normal peripheral blood lymphocytes. Low levels of J chain were also detected by RIA in lysates of leukemic null and pre-B cells. Most of the intracellular J chain became detectable after reduction and alkylation of cell lysates, and free J chain was not found in the culture supernatants. The amount of intracellular and secreted immunoglobulin-bound J chain increased dramatically after PWM stimulation of peripheral blood lymphocytes. The majority of J chain- positive cells seen over an 8 d culture interval were lymphocytes and lymphoblasts, while mu chain was found primarily in plasma cells. These results suggest that J chain expression precedes mu chain synthesis during B cell differentiation and that a combination of the two chains for secretion is not initiated until the onset of plasma cells maturation.

Full Text

The Full Text of this article is available as a PDF (3.7 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Balch C. M., Dougherty P. A., Vogler L. B., Ades E. W., Ferrone S. A new B cell differentiation antigen (BDA) on normal and leukemic human B lymphocytes that is distinct from known DR (Ia-like) antigens. J Immunol. 1978 Dec;121(6):2322–2328. [PubMed] [Google Scholar]
  2. Brandtzaeg P., Gjeruldsen S. T., Korsrud F., Baklien K., Berdal P., Ek J. The human secretory immune system shows striking heterogeneity with regard to involvement of J chain-positive IgD immunocytes. J Immunol. 1979 Feb;122(2):503–510. [PubMed] [Google Scholar]
  3. Brandtzaeg P. Presence of J chain in human immunocytes containing various immunoglobulin classes. Nature. 1974 Nov 29;252(5482):418–420. doi: 10.1038/252418a0. [DOI] [PubMed] [Google Scholar]
  4. Brandtzaeg P. Studies on J chain and binding site for secretory component in circulating human B cells. II. The cytoplasm. Clin Exp Immunol. 1976 Jul;25(1):59–66. [PMC free article] [PubMed] [Google Scholar]
  5. Chapuis R. M., Koshland M. E. Mechanism of IgM polymerization. Proc Natl Acad Sci U S A. 1974 Mar;71(3):657–661. doi: 10.1073/pnas.71.3.657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Della Corte E., Parkhouse R. M. Biosynthesis of immunoglobulin A (IgA) and immunoglobulin M (IgM). Requirement for J chain and a disulphide-exchanging enzyme for polymerization. Biochem J. 1973 Nov;136(3):597–606. doi: 10.1042/bj1360597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Findley H. W., Jr, Cooper M. D., Kim T. H., Alvarado C., Ragab A. H. Two new acute lymphoblastic leukemia cell lines with early B-cell phenotypes. Blood. 1982 Dec;60(6):1305–1309. [PubMed] [Google Scholar]
  8. Gathings W. E., Lawton A. R., Cooper M. D. Immunofluorescent studies of the development of pre-B cells, B lymphocytes and immunoglobulin isotype diversity in humans. Eur J Immunol. 1977 Nov;7(11):804–810. doi: 10.1002/eji.1830071112. [DOI] [PubMed] [Google Scholar]
  9. Graham R. C., Jr, Karnovsky M. J. The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney: ultrastructural cytochemistry by a new technique. J Histochem Cytochem. 1966 Apr;14(4):291–302. doi: 10.1177/14.4.291. [DOI] [PubMed] [Google Scholar]
  10. Hajdu I. The immunohistochemical detection of J chain in lymphoid cells in tissue sections: the necessity of trypsin digestion. Cell Immunol. 1983 Jul 1;79(1):157–163. doi: 10.1016/0008-8749(83)90058-8. [DOI] [PubMed] [Google Scholar]
  11. Hall J. G., Birbeck M. S., Robertson D., Peppard J., Orlans E. The use of detergents and immunoperoxidase reagents for the ultrastructural demonstration of internal immunoglobulin in lymph cells. J Immunol Methods. 1978;19(4):351–359. doi: 10.1016/0022-1759(78)90019-4. [DOI] [PubMed] [Google Scholar]
  12. Halpern M. S., Coffman R. L. Polymer formation and J chain synthesis in mouse plasmacytomas. J Immunol. 1972 Oct;109(4):674–680. [PubMed] [Google Scholar]
  13. Hauptman S. P., Tomasi T. B., Jr Mechanism of immunoglobulin A polymerization. J Biol Chem. 1975 May 25;250(10):3891–3896. [PubMed] [Google Scholar]
  14. Kaji H., Parkhouse M. E. Control of J chain biosynthesis in relation to heavy and light chain synthesis, polymerization and secretion. J Immunol. 1975 Apr;114(4):1218–1220. [PubMed] [Google Scholar]
  15. Korsmeyer S. J., Arnold A., Bakhshi A., Ravetch J. V., Siebenlist U., Hieter P. A., Sharrow S. O., LeBien T. W., Kersey J. H., Poplack D. G. Immunoglobulin gene rearrangement and cell surface antigen expression in acute lymphocytic leukemias of T cell and B cell precursor origins. J Clin Invest. 1983 Feb;71(2):301–313. doi: 10.1172/JCI110770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Korsmeyer S. J., Hieter P. A., Ravetch J. V., Poplack D. G., Waldmann T. A., Leder P. Developmental hierarchy of immunoglobulin gene rearrangements in human leukemic pre-B-cells. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7096–7100. doi: 10.1073/pnas.78.11.7096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kubagawa H., Mayumi M., Crist W. M., Cooper M. D. Immunoglobulin heavy-chain switching in pre-B leukaemias. Nature. 1983 Jan 27;301(5898):340–342. doi: 10.1038/301340a0. [DOI] [PubMed] [Google Scholar]
  18. Kutteh W. H., Prince S. J., Phillips J. O., Spenney J. G., Mestecky J. Properties of immunoglobulin A in serum of individuals with liver diseases and in hepatic bile. Gastroenterology. 1982 Feb;82(2):184–193. [PubMed] [Google Scholar]
  19. Lane M. A., Sainten A., Cooper G. M. Stage-specific transforming genes of human and mouse B- and T-lymphocyte neoplasms. Cell. 1982 Apr;28(4):873–880. doi: 10.1016/0092-8674(82)90066-6. [DOI] [PubMed] [Google Scholar]
  20. Levitt D., Cooper M. D. Mouse pre-B cells synthesize and secrete mu heavy chains but not light chains. Cell. 1980 Mar;19(3):617–625. doi: 10.1016/s0092-8674(80)80038-9. [DOI] [PubMed] [Google Scholar]
  21. Mason D. Y., Stein H. Reactive and neoplastic human lymphoid cells producing J chain in the absence of immunoglobulin: evidence for the existence of 'J chain disease'? Clin Exp Immunol. 1981 Nov;46(2):305–312. [PMC free article] [PubMed] [Google Scholar]
  22. Mather E. L., Alt F. W., Bothwell A. L., Baltimore D., Koshland M. E. Expression of J chain RNA in cell lines representing different stages of B lymphocyte differentiation. Cell. 1981 Feb;23(2):369–378. doi: 10.1016/0092-8674(81)90132-x. [DOI] [PubMed] [Google Scholar]
  23. McCune J. M., Fu S. M., Kunkel H. G. J chain biosynthesis in pre-B cells and other possible precursor B cells. J Exp Med. 1981 Jul 1;154(1):138–145. doi: 10.1084/jem.154.1.138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mestecky J., Preud'homme J. L., Crago S. S., Mihaesco E., Prchal J. T., Okos A. J. Presence of J chain in human lymphoid cells. Clin Exp Immunol. 1980 Feb;39(2):371–385. [PMC free article] [PubMed] [Google Scholar]
  25. Mestecky J., Winchester R. J., Hoffman T., Kunkel H. G. Parallel synthesis of immunoglobulins and J chain in pokeweed mitogen-stimulated normal cells and in lymphoblastoid cell lines. J Exp Med. 1977 Mar 1;145(3):760–765. doi: 10.1084/jem.145.3.760. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mestecky J., Zikan J., Butler W. T., Kulhavy R. Studies on human secretory immunoglobulin A. 3. J chain. Immunochemistry. 1972 Sep;9(9):883–890. doi: 10.1016/0019-2791(72)90162-0. [DOI] [PubMed] [Google Scholar]
  27. Mosmann T., Baumal R. Synthesis but not secretion of J chain by variant mouse myeloma cells which lose alpha-chain-synthesizing ability. J Immunol. 1975 Oct;115(4):955–962. [PubMed] [Google Scholar]
  28. Nadler L. M., Ritz J., Hardy R., Pesando J. M., Schlossman S. F., Stashenko P. A unique cell surface antigen identifying lymphoid malignancies of B cell origin. J Clin Invest. 1981 Jan;67(1):134–140. doi: 10.1172/JCI110005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Nagura H., Brandtzaeg P., Nakane P. K., Brown W. R. Ultrastructural localization of J chain in human intestinal mucosa. J Immunol. 1979 Sep;123(3):1044–1050. [PubMed] [Google Scholar]
  30. Nakane P. K., Kawaoi A. Peroxidase-labeled antibody. A new method of conjugation. J Histochem Cytochem. 1974 Dec;22(12):1084–1091. doi: 10.1177/22.12.1084. [DOI] [PubMed] [Google Scholar]
  31. Owen J. J., Wright D. E., Habu S., Raff M. C., Cooper M. D. Studies on the generation of B lymphocytes in fetal liver and bone marrow. J Immunol. 1977 Jun;118(6):2067–2072. [PubMed] [Google Scholar]
  32. Radl J., Schuit H. R., Mestecky J., Hijmans W. The origin of monomeric and polymeric forms of IgA in man. Adv Exp Med Biol. 1974;45(0):57–65. doi: 10.1007/978-1-4613-4550-3_7. [DOI] [PubMed] [Google Scholar]
  33. Raff M. C., Megson M., Owen J. J., Cooper M. D. Early production of intracellular IgM by B-lymphocyte precursors in mouse. Nature. 1976 Jan 22;259(5540):224–226. doi: 10.1038/259224a0. [DOI] [PubMed] [Google Scholar]
  34. Roth R. A., Koshland M. E. Role of disulfide interchange enzyme in immunoglobulin synthesis. Biochemistry. 1981 Nov 10;20(23):6594–6599. doi: 10.1021/bi00526a012. [DOI] [PubMed] [Google Scholar]
  35. Seligmann M., Vogler L. B., Preud'Homme J. L., Guglielmi P., Brouet J. C. Immunological phenotypes of human leukemias of the B-cell lineage. Blood Cells. 1981;7(2):237–246. [PubMed] [Google Scholar]
  36. Vogler L. B., Crist W. M., Bockman D. E., Pearl E. R., Lawton A. R., Cooper M. D. Pre-B-cell leukemia. A new phenotype of childhood lymphoblastic leukemia. N Engl J Med. 1978 Apr 20;298(16):872–878. doi: 10.1056/NEJM197804202981603. [DOI] [PubMed] [Google Scholar]
  37. Yagi M., D'Eustachio P., Ruddle F. H., Koshland M. E. J chain is encoded by a single gene unlinked to other immunoglobulin structural genes. J Exp Med. 1982 Mar 1;155(3):647–654. doi: 10.1084/jem.155.3.647. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES