Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1984 Apr;115(1):117–124.

Low-grade lymphomas. Expression of developmentally regulated B-cell antigens.

J Cossman, L M Neckers, S Hsu, D Longo, E S Jaffe
PMCID: PMC1900345  PMID: 6201073

Abstract

A series of low-grade B-cell lymphomas was analyzed for a battery of immunologic determinants by flow cytometry and immunohistochemistry. Histologically distinctive subclasses of these lymphomas, well-differentiated lymphocytic (WDL), intermediately differentiated lymphocytic (IDL), and follicular center cell (FCC) lymphoma, were found to be readily distinguishable by their expression of immunologic determinants that are known to be developmentally regulated in normal B cells. Although all cases expressed monoclonal surface immunoglobulin (sIg), HLA-DR, and the surface membrane proteins recognized by antibodies B1 (p32) and BA1, staining with other monoclonal antibodies revealed unique immunologic phenotypes for each subclass: WDL p65 (Leu 1)+, p24 (BA2)-; IDL p65+, p24+; FCC p65-, p24-. Additionally, the fluorescence intensities (number of determinants per cell) obtained for sIg, BA-1, and B1, but not HLA-DR, were significantly different among the three lymphoma subclasses. The relative fluorescence intensities of each of these three markers followed the same pattern: FCC greater than IDL greater than WDL. Taken together, these distinguishing features suggest that low-grade B-cell lymphomas represent arrested, and possibly sequential, stages of B-cell differentiation.

Full text

PDF
119

Images in this article

119Figure 1
on p.119

Selected References

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

  1. Abramson C. S., Kersey J. H., LeBien T. W. A monoclonal antibody (BA-1) reactive with cells of human B lymphocyte lineage. J Immunol. 1981 Jan;126(1):83–88. [PubMed] [Google Scholar]
  2. Alt F. W., Bothwell A. L., Knapp M., Siden E., Mather E., Koshland M., Baltimore D. Synthesis of secreted and membrane-bound immunoglobulin mu heavy chains is directed by mRNAs that differ at their 3' ends. Cell. 1980 Jun;20(2):293–301. doi: 10.1016/0092-8674(80)90615-7. [DOI] [PubMed] [Google Scholar]
  3. Boumsell L., Coppin H., Pham D., Raynal B., Lemerle J., Dausset J., Bernard A. An antigen shared by a human T cell subset and B cell chronic lymphocytic leukemic cells. Distribution on normal and malignant lymphoid cells. J Exp Med. 1980 Jul 1;152(1):229–234. doi: 10.1084/jem.152.1.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Braun M. P., Martin P. J., Ledbetter J. A., Hansen J. A. Granulocytes and cultured human fibroblasts express common acute lymphoblastic leukemia-associated antigens. Blood. 1983 Apr;61(4):718–725. [PubMed] [Google Scholar]
  5. Burns B. F., Warnke R. A., Doggett R. S., Rouse R. V. Expression of a T-cell antigen (Leu-1) by B-cell lymphomas. Am J Pathol. 1983 Nov;113(2):165–171. [PMC free article] [PubMed] [Google Scholar]
  6. Caligaris-Cappio F., Gobbi M., Bofill M., Janossy G. Infrequent normal B lymphocytes express features of B-chronic lymphocytic leukemia. J Exp Med. 1982 Feb 1;155(2):623–628. doi: 10.1084/jem.155.2.623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cossman J., Jaffe E. S. Distribution of complement receptor subtypes in non-Hodgkin's lymphomas of B-cell origin. Blood. 1981 Jul;58(1):20–26. [PubMed] [Google Scholar]
  8. Cossman J., Neckers L. M., Arnold A., Korsmeyer S. J. Induction of differentiation in a case of common acute lymphoblastic leukemia. N Engl J Med. 1982 Nov 11;307(20):1251–1254. doi: 10.1056/NEJM198211113072006. [DOI] [PubMed] [Google Scholar]
  9. Cossman J., Neckers L. M., Leonard W. J., Greene W. C. Polymorphonuclear neutrophils express the common acute lymphoblastic leukemia antigen. J Exp Med. 1983 Mar 1;157(3):1064–1069. doi: 10.1084/jem.157.3.1064. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Davis M. M., Calame K., Early P. W., Livant D. L., Joho R., Weissman I. L., Hood L. An immunoglobulin heavy-chain gene is formed by at least two recombinational events. Nature. 1980 Feb 21;283(5749):733–739. doi: 10.1038/283733a0. [DOI] [PubMed] [Google Scholar]
  11. Engleman E. G., Warnke R., Fox R. I., Dilley J., Benike C. J., Levy R. Studies of a human T lymphocyte antigen recognized by a monoclonal antibody. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1791–1795. doi: 10.1073/pnas.78.3.1791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ferrarini M., Viale G., Risso A., Pernis B. A study of immunoglobulin classes present on the membrane and in the cytoplasm of human tonsil plasma cells. Eur J Immunol. 1976 Aug;6(8):562–565. doi: 10.1002/eji.1830060807. [DOI] [PubMed] [Google Scholar]
  13. Fu S. M., Chiorazzi N., Kunkel H. G., Halper J. P., Harris S. R. Induction of in vitro differentiation and immunoglobulin synthesis of human leukemic B lymphocytes. J Exp Med. 1978 Dec 1;148(6):1570–1578. doi: 10.1084/jem.148.6.1570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Garvin A. J., Simon R., Young R. C., DeVita V. T., Berard C. W. The Rappaport classification of non-Hodgkin's lymphomas: a closer look using other proposed classifications. Semin Oncol. 1980 Sep;7(3):234–243. [PubMed] [Google Scholar]
  15. Gormus B. J., Crandall R. B., Shands J. W., Jr Endotoxin-stimulated spleen cells: mitogenesis, the occurrence of the C3 receptor, and the production of immunoglobulin. J Immunol. 1974 Feb;112(2):770–775. [PubMed] [Google Scholar]
  16. Halper J., Fu S. M., Wang C. Y., Winchester R., Kunkel H. G. Patterns of expression of human "Ia-like" antigens during the terminal stages of B cell development. J Immunol. 1978 May;120(5):1480–1484. [PubMed] [Google Scholar]
  17. Harris N. L., Bhan A. K. Distribution of T-cell subsets in follicular and diffuse lymphomas of B-cell type. Am J Pathol. 1983 Nov;113(2):172–180. [PMC free article] [PubMed] [Google Scholar]
  18. Hieter P. A., Korsmeyer S. J., Waldmann T. A., Leder P. Human immunoglobulin kappa light-chain genes are deleted or rearranged in lambda-producing B cells. Nature. 1981 Apr 2;290(5805):368–372. doi: 10.1038/290368a0. [DOI] [PubMed] [Google Scholar]
  19. Hsu S. M., Raine L., Fanger H. A comparative study of the peroxidase-antiperoxidase method and an avidin-biotin complex method for studying polypeptide hormones with radioimmunoassay antibodies. Am J Clin Pathol. 1981 May;75(5):734–738. doi: 10.1093/ajcp/75.5.734. [DOI] [PubMed] [Google Scholar]
  20. Jaffe E. S., Shevach E. M., Frank M. M., Berard C. W., Green I. Nodular lymphoma--evidence for origin from follicular B lymphocytes. N Engl J Med. 1974 Apr 11;290(15):813–819. doi: 10.1056/NEJM197404112901501. [DOI] [PubMed] [Google Scholar]
  21. Kamoun M., Martin P. J., Hansen J. A., Brown M. A., Siadak A. W., Nowinski R. C. Identification of a human T lymphocyte surface protein associated with the E-rosette receptor. J Exp Med. 1981 Jan 1;153(1):207–212. doi: 10.1084/jem.153.1.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kersey J. H., LeBien T. W., Abramson C. S., Newman R., Sutherland R., Greaves M. P-24: a human leukemia-associated and lymphohemopoietic progenitor cell surface structure identified with monoclonal antibody. J Exp Med. 1981 Mar 1;153(3):726–731. doi: 10.1084/jem.153.3.726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Knowles D. M., 2nd, Halper J. P., Azzo W., Wang C. Y. Reactivity of monoclonal antibodies Leu 1 and OKT1 with malignant human lymphoid cells. Correlation with conventional cell markers. Cancer. 1983 Oct 15;52(8):1369–1377. doi: 10.1002/1097-0142(19831015)52:8<1369::aid-cncr2820520806>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. LeBien T. W., Bollum F. J., Yasmineh W. G., Kersey J. H. Phorbol ester-induced differentiation of a non-T, non-B leukemic cell line: model for human lymphoid progenitor cell development. J Immunol. 1982 Mar;128(3):1316–1320. [PubMed] [Google Scholar]
  26. Mann R. B., Jaffe E. S., Berard C. W. Malignant lymphomas--a conceptual understanding of morphologic diversity. A review. Am J Pathol. 1979 Jan;94(1):105–192. [PMC free article] [PubMed] [Google Scholar]
  27. Martin P. J., Hansen J. A., Nowinski R. C., Brown M. A. A new human T-cell differentiation antigen: unexpected expression on chronic lymphocytic leukemia cells. Immunogenetics. 1980;11(5):429–439. doi: 10.1007/BF01567812. [DOI] [PubMed] [Google Scholar]
  28. Miller R. A., Maloney D. G., Warnke R., Levy R. Treatment of B-cell lymphoma with monoclonal anti-idiotype antibody. N Engl J Med. 1982 Mar 4;306(9):517–522. doi: 10.1056/NEJM198203043060906. [DOI] [PubMed] [Google Scholar]
  29. Nanba K., Jaffe E. S., Braylan R. C., Soban E. J., Berard C. W. Alkaline phosphatase-positive malignant lymphoma. A subtype of B-cell lymphomas. Am J Clin Pathol. 1977 Nov;68(5):535–542. doi: 10.1093/ajcp/68.5.535. [DOI] [PubMed] [Google Scholar]
  30. Osborne C. K., Norton L., Young R. C., Garvin A. J., Simon R. M., Berard C. W., Hubbard S., DeVita V. T., Jr Nodular histiocytic lymphoma: an aggressive nodular lymphoma with potential for prolonged disease-free survival. Blood. 1980 Jul;56(1):98–103. [PubMed] [Google Scholar]
  31. Pangalis G. A., Nathwani B. N., Rappaport H. Malignant lymphoma, well differentiated lymphocytic: its relationship with chronic lymphocytic leukemia and macroglobulinemia of Waldenström. Cancer. 1977 Mar;39(3):999–1010. doi: 10.1002/1097-0142(197703)39:3<999::aid-cncr2820390302>3.0.co;2-r. [DOI] [PubMed] [Google Scholar]
  32. Poppema S., Bhan A. K., Reinherz E. L., McCluskey R. T., Schlossman S. F. Distribution of T cell subsets in human lymph nodes. J Exp Med. 1981 Jan 1;153(1):30–41. doi: 10.1084/jem.153.1.30. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Rabbitts T. H. Evidence for splicing of interrupted immunoglobulin variable and constant region sequences in nuclear RNA. Nature. 1978 Sep 28;275(5678):291–296. doi: 10.1038/275291a0. [DOI] [PubMed] [Google Scholar]
  34. Reinherz E. L., Kung P. C., Goldstein G., Levey R. H., Schlossman S. F. Discrete stages of human intrathymic differentiation: analysis of normal thymocytes and leukemic lymphoblasts of T-cell lineage. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1588–1592. doi: 10.1073/pnas.77.3.1588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Ritz J., Nadler L. M., Bhan A. K., Notis-McConarty J., Pesando J. M., Schlossman S. F. Expression of common acute lymphoblastic leukemia antigen (CALLA) by lymphomas of B-cell and T-cell lineage. Blood. 1981 Sep;58(3):648–652. [PubMed] [Google Scholar]
  36. Ritz J., Pesando J. M., Notis-McConarty J., Lazarus H., Schlossman S. F. A monoclonal antibody to human acute lymphoblastic leukaemia antigen. Nature. 1980 Feb 7;283(5747):583–585. doi: 10.1038/283583a0. [DOI] [PubMed] [Google Scholar]
  37. Robèrt K. H., Möller E., Gahrton G., Eriksson H., Nilsson B. B-cell activation of peripheral blood lymphocytes from patients with chronic lymphatic leukaemia. Clin Exp Immunol. 1978 Aug;33(2):302–308. [PMC free article] [PubMed] [Google Scholar]
  38. Rogers J., Early P., Carter C., Calame K., Bond M., Hood L., Wall R. Two mRNAs with different 3' ends encode membrane-bound and secreted forms of immunoglobulin mu chain. Cell. 1980 Jun;20(2):303–312. doi: 10.1016/0092-8674(80)90616-9. [DOI] [PubMed] [Google Scholar]
  39. Royston I., Majda J. A., Baird S. M., Meserve B. L., Griffiths J. C. Human T cell antigens defined by monoclonal antibodies: the 65,000-dalton antigen of T cells (T65) is also found on chronic lymphocytic leukemia cells bearing surface immunoglobulin. J Immunol. 1980 Aug;125(2):725–731. [PubMed] [Google Scholar]
  40. Saiki O., Kishimoto T., Kuritani T., Muraguchi A., Yamamura Y. In vitro induction of IgM secretion and switching to IgG production in human B leukemic cells with the help of T cells. J Immunol. 1980 Jun;124(6):2609–2614. [PubMed] [Google Scholar]
  41. Salmon S. E., Seligmann M. B-cell neoplasia in man. Lancet. 1974 Nov 23;2(7891):1230–1233. doi: 10.1016/s0140-6736(74)90748-x. [DOI] [PubMed] [Google Scholar]
  42. Slease R. B., Wistar R., Jr, Scher I. Surface immunoglobulin density on human peripheral blood mononuclear cells. Blood. 1979 Jul;54(1):72–87. [PubMed] [Google Scholar]
  43. Stashenko P., Nadler L. M., Hardy R., Schlossman S. F. Characterization of a human B lymphocyte-specific antigen. J Immunol. 1980 Oct;125(4):1678–1685. [PubMed] [Google Scholar]
  44. Stashenko P., Nadler L. M., Hardy R., Schlossman S. F. Expression of cell surface markers after human B lymphocyte activation. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3848–3852. doi: 10.1073/pnas.78.6.3848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Stein H., Gerdes J., Mason D. Y. The normal and malignant germinal centre. Clin Haematol. 1982 Oct;11(3):531–559. [PubMed] [Google Scholar]
  46. Stein R. S., Cousar J., Flexner J. M., Graber S. E., McKee L. C., Krantz S., Collins R. C. Malignant lymphomas of follicular center cell origin in man. III. Prognostic features. Cancer. 1979 Dec;44(6):2236–2243. doi: 10.1002/1097-0142(197912)44:6<2236::aid-cncr2820440635>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
  47. Swerdlow S. H., Habeshaw J. A., Murray L. J., Dhaliwal H. S., Lister T. A., Stansfeld A. G. Centrocytic lymphoma: a distinct clinicopathologic and immunologic entity. A multiparameter study of 18 cases at diagnosis and relapse. Am J Pathol. 1983 Nov;113(2):181–197. [PMC free article] [PubMed] [Google Scholar]
  48. Weisenburger D. D., Nathwani B. N., Diamond L. W., Winberg C. D., Rappaport H. Malignant lymphoma, intermediate lymphocytic type: a clinicopathologic study of 42 cases. Cancer. 1981 Sep 15;48(6):1415–1425. doi: 10.1002/1097-0142(19810915)48:6<1415::aid-cncr2820480625>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
  49. Yuan D., Tucker P. W. Effect of lipopolysaccharide stimulation on the transcription and translation of messenger RNA for cell surface immunoglobulin M. J Exp Med. 1982 Oct 1;156(4):962–974. doi: 10.1084/jem.156.4.962. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES