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. 1985 Sep;120(3):356–370.

SIg-E- ("null-cell") non-Hodgkin's lymphomas. Multiparametric determination of their B- or T-cell lineage.

D M Knowles 2nd, L Dodson, J S Burke, J M Wang, F Bonetti, P G Pelicci, F Flug, R Dalla-Favera, C Y Wang
PMCID: PMC1887976  PMID: 2931028

Abstract

The authors performed immunophenotypic, functional, and molecular analysis of the neoplastic cells from 20 cases of SIg-, E-("null-cell") non-Hodgkin's lymphoma (NHL) in order to determine their lineage, better define this category of NHL, and evaluate the lineage specificity of selected phenotypic markers and the individual and collective utility of these approaches. They assigned 4 cases to the T-cell lineage, and 15 cases to the B-cell lineage, and 1 case remained indeterminant on the basis of immunophenotypic analysis. The cells from 2 cases assigned to the T-cell lineage expressed unusual phenotypes, but their T-cell derivation was confirmed by the demonstration of helper function in vitro. The 15 cases assigned to the B-cell lineage expressed a variety of B-cell-associated antigens, consistent with various stages of B-cell differentiation. Monoclonal antibodies OKT3, OKT4, OKT6, and OKT8 exhibited T-cell lineage restriction; and monoclonal antibodies OKB2, BL1, and B1 exhibited B-cell lineage restriction. Ia, TdT, cALLa, OKT9, and OKT10 exhibited lineage infidelity. Southern blot analysis for immunoglobulin heavy chain gene rearrangements confirmed 18 of the 19 lineage assignments made by immunophenotypic analysis and suggested that the 1 case of indeterminate phenotype was a B-cell neoplasm. One T-cell (OKT3+, T4+) neoplasm exhibited rearranged immunoglobulin heavy chain genes. Thus, neither immunophenotypic analysis nor the demonstration of rearranged immunoglobulin heavy chain genes alone permitted the satisfactory lineage assignment of every case of SIg-, E- NHL. However, combined immunophenotypic, functional, and genotypic analysis allowed us to assign every SIg-, E-NHL to the B- or T-cell lineage and to demonstrate that truly "null-cell" NHLs are probably very uncommon.

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Selected References

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  1. Aisenberg A. C., Wilkes B. M. Unusual human lymphoma phenotype defined by monoclonal antibody. J Exp Med. 1980 Oct 1;152(4):1126–1131. doi: 10.1084/jem.152.4.1126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arnold A., Cossman J., Bakhshi A., Jaffe E. S., Waldmann T. A., Korsmeyer S. J. Immunoglobulin-gene rearrangements as unique clonal markers in human lymphoid neoplasms. N Engl J Med. 1983 Dec 29;309(26):1593–1599. doi: 10.1056/NEJM198312293092601. [DOI] [PubMed] [Google Scholar]
  3. Battifora H., Trowbridge I. S. A monoclonal antibody useful for the differential diagnosis between malignant lymphoma and nonhematopoietic neoplasms. Cancer. 1983 Mar 1;51(5):816–821. doi: 10.1002/1097-0142(19830301)51:5<816::aid-cncr2820510512>3.0.co;2-4. [DOI] [PubMed] [Google Scholar]
  4. Berard C. W., Greene M. H., Jaffe E. S., Magrath I., Ziegler J. NIH conference. A multidisciplinary approach to non-hodgkin's lymphomas. Ann Intern Med. 1981 Feb;94(2):218–235. doi: 10.7326/0003-4819-94-2-218. [DOI] [PubMed] [Google Scholar]
  5. Bloomfield C. D., Gajl-Peczalska K. J., Frizzera G., Kersey J. H., Goldman A. I. Clinical utility of lymphocyte surface markers combined with the Lukes-Collins histologic classification in adult lymphoma. N Engl J Med. 1979 Sep 6;301(10):512–518. doi: 10.1056/NEJM197909063011002. [DOI] [PubMed] [Google Scholar]
  6. Breard J., Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. A monoclonal antibody reactive with human peripheral blood monocytes. J Immunol. 1980 Apr;124(4):1943–1948. [PubMed] [Google Scholar]
  7. 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]
  8. Catovsky D., Greaves M. F., Rose M., Galton D. A., Goolden A. W., McCluskey D. R., White J. M., Lampert I., Bourikas G., Ireland R. Adult T-cell lymphoma-leukaemia in Blacks from the West Indies. Lancet. 1982 Mar 20;1(8273):639–643. doi: 10.1016/s0140-6736(82)92200-0. [DOI] [PubMed] [Google Scholar]
  9. Cossman J., Neckers L. M., Hsu S., Longo D., Jaffe E. S. Low-grade lymphomas. Expression of developmentally regulated B-cell antigens. Am J Pathol. 1984 Apr;115(1):117–124. [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Foon K. A., Schroff R. W., Gale R. P. Surface markers on leukemia and lymphoma cells: recent advances. Blood. 1982 Jul;60(1):1–19. [PubMed] [Google Scholar]
  12. Greaves M. F., Janossy G., Peto J., Kay H. Immunologically defined subclasses of acute lymphoblastic leukaemia in children: their relationship to presentation features and prognosis. Br J Haematol. 1981 Jun;48(2):179–197. [PubMed] [Google Scholar]
  13. Greaves M. F., Rao J., Hariri G., Verbi W., Catovsky D., Kung P., Goldstein G. Phenotypic heterogeneity and cellular origins of T cell malignancies. Leuk Res. 1981;5(4-5):281–299. doi: 10.1016/0145-2126(81)90001-1. [DOI] [PubMed] [Google Scholar]
  14. Ha K., Minden M., Hozumi N., Gelfand E. W. Immunoglobulin mu-chain gene rearrangement in a patient with T cell acute lymphoblastic leukemia. J Clin Invest. 1984 Apr;73(4):1232–1236. doi: 10.1172/JCI111310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Halper J. P., Knowles D. M., 2nd, Wang C. Y. Ia antigen expression by human malignant lymphomas: correlation with conventional lymphoid markers. Blood. 1980 Mar;55(3):373–382. [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. Hattori T., Uchiyama T., Toibana T., Takatsuki K., Uchino H. Surface phenotype of Japanese adult T-cell leukemia cells characterized by monoclonal antibodies. Blood. 1981 Sep;58(3):645–647. [PubMed] [Google Scholar]
  18. Haynes B. F., Hensley L. L., Jegasothy B. V. Phenotypic characterization of skin-infiltrating T cells in cutaneous T-cell lymphoma: comparison with benign cutaneous T-cell infiltrates. Blood. 1982 Aug;60(2):463–473. [PubMed] [Google Scholar]
  19. Hofman F. M., Meyer P. R., Yanagihara E., Modlin R. L., Rea T. H., Parker J. W., Lukes R. J., Taylor C. R. Demonstration of a subpopulation of Ia+ T-helper cells in mycosis fungoides and the Sézary syndrome. Am J Dermatopathol. 1983 Apr;5(2):135–143. doi: 10.1097/00000372-198304000-00011. [DOI] [PubMed] [Google Scholar]
  20. Jaffe E. S., Strauchen J. A., Berard C. W. Predictability of immunologic phenotype by morphologic criteria in diffuse aggressive non-Hodgkin's lymphomas. Am J Clin Pathol. 1982 Jan;77(1):46–49. doi: 10.1093/ajcp/77.1.46. [DOI] [PubMed] [Google Scholar]
  21. Kitchingman G. R., Rovigatti U., Mauer A. M., Melvin S., Murphy S. B., Stass S. Rearrangement of immunoglobulin heavy chain genes in T cell acute lymphoblastic leukemia. Blood. 1985 Mar;65(3):725–729. [PubMed] [Google Scholar]
  22. 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]
  23. Knowles D. M., 2nd, Halper J. P. Human T-cell malignancies: Correlative clinical, histopathologic, immunologic, and cytochemical analysis of 23 cases. Am J Pathol. 1982 Feb;106(2):187–203. [PMC free article] [PubMed] [Google Scholar]
  24. Knowles D. M., 2nd, Tolidjian B., Marboe C. C., Halper J. P., Azzo W., Wang C. Y. A new human B-lymphocyte surface antigen (BL 2) detectable by a hybridoma monoclonal antibody: distribution on benign and malignant lymphoid cells. Blood. 1983 Jul;62(1):191–199. [PubMed] [Google Scholar]
  25. Knowles D. M., 2nd, Tolidjian B., Marboe C. C., Mittler R. S., Talle M. A., Goldstein G. Distribution of antigens defined by OKB monoclonal antibodies on benign and malignant lymphoid cells and on nonlymphoid tissues. Blood. 1984 Apr;63(4):886–896. [PubMed] [Google Scholar]
  26. 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]
  27. 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]
  28. Lukes R. J., Collins R. D. Immunologic characterization of human malignant lymphomas. Cancer. 1974 Oct;34(4 Suppl):suppl–suppl:1503. doi: 10.1002/1097-0142(197410)34:8+<1488::aid-cncr2820340822>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
  29. Lukes R. J., Taylor C. R., Parker J. W., Lincoln T. L., Pattengale P. K., Tindle B. H. A morphologic and immunologic surface marker study of 299 cases of non-Hodgkin lymphomas and related leukemias. Am J Pathol. 1978 Feb;90(2):461–486. [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Miedema F., Terpstra F. G., Smit J. W., Daenen S., Gerrits W., Hegde U., Matutes E., Catovsky D., Greaves M. F., Melief C. J. Functional properties of neoplastic T cells in adult T cell lymphoma/leukemia patients from the Caribbean. Blood. 1984 Feb;63(2):477–481. [PubMed] [Google Scholar]
  32. Mittler R. S., Talle M. A., Carpenter K., Rao P. E., Goldstein G. Generation and characterization of monoclonal antibodies reactive with human B lymphocytes. J Immunol. 1983 Oct;131(4):1754–1761. [PubMed] [Google Scholar]
  33. Murphy G. F., Bhan A. K., Sato S., Mihm M. C., Jr, Harrist T. J. A new immunologic marker for human Langerhans cells. N Engl J Med. 1981 Mar 26;304(13):791–792. doi: 10.1056/NEJM198103263041320. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. Pinkus G. S., Said J. W. Characterization of non-Hodgkin's lymphomas using multiple cell markers. Immunologic, morphologic, and cytochemical studies of 72 cases. Am J Pathol. 1979 Feb;94(2):349–380. [PMC free article] [PubMed] [Google Scholar]
  36. Rao P. E., Talle M. A., Kung P. C., Goldstein G. Five epitopes of a differentiation antigen on human inducer T cells distinguished by monoclonal antibodies. Cell Immunol. 1983 Sep;80(2):310–319. doi: 10.1016/0008-8749(83)90119-3. [DOI] [PubMed] [Google Scholar]
  37. Ravetch J. V., Siebenlist U., Korsmeyer S., Waldmann T., Leder P. Structure of the human immunoglobulin mu locus: characterization of embryonic and rearranged J and D genes. Cell. 1981 Dec;27(3 Pt 2):583–591. doi: 10.1016/0092-8674(81)90400-1. [DOI] [PubMed] [Google Scholar]
  38. Reinherz E. L., Schlossman S. F. Current concepts in immunology: Regulation of the immune response--inducer and suppressor T-lymphocyte subsets in human beings. N Engl J Med. 1980 Aug 14;303(7):370–373. doi: 10.1056/NEJM198008143030704. [DOI] [PubMed] [Google Scholar]
  39. Reinherz E. L., Schlossman S. F. The differentiation and function of human T lymphocytes. Cell. 1980 Apr;19(4):821–827. doi: 10.1016/0092-8674(80)90072-0. [DOI] [PubMed] [Google Scholar]
  40. 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]
  41. 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]
  42. Rogozinski L., Bass A., Glickman E., Talle M. A., Goldstein G., Wang J., Chess L., Thomas Y. The T4 surface antigen is involved in the induction of helper function. J Immunol. 1984 Feb;132(2):735–739. [PubMed] [Google Scholar]
  43. Shen H. H., Talle M. A., Goldstein G., Chess L. Functional subsets of human monocytes defined by monoclonal antibodies: a distinct subset of monocytes contains the cells capable of inducing the autologous mixed lymphocyte culture. J Immunol. 1983 Feb;130(2):698–705. [PubMed] [Google Scholar]
  44. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  45. 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]
  46. Talle M. A., Allegar N., Makowski M., Rao P. E., Mittler R. S., Goldstein G. Classification of human lymphocytes and monocytes with the OK series of monoclonal antibodies. Diagn Immunol. 1983;1(3):129–135. [PubMed] [Google Scholar]
  47. Talle M. A., Rao P. E., Westberg E., Allegar N., Makowski M., Mittler R. S., Goldstein G. Patterns of antigenic expression on human monocytes as defined by monoclonal antibodies. Cell Immunol. 1983 May;78(1):83–99. doi: 10.1016/0008-8749(83)90262-9. [DOI] [PubMed] [Google Scholar]
  48. Thomas Y., Rogozinski L., Irigoyen O. H., Friedman S. M., Kung P. C., Goldstein G., Chess L. Functional analysis of human T cell subsets defined by monoclonal antibodies. IV. Induction of suppressor cells within the OKT4+ population. J Exp Med. 1981 Aug 1;154(2):459–467. doi: 10.1084/jem.154.2.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Wahl G. M., Stern M., Stark G. R. Efficient transfer of large DNA fragments from agarose gels to diazobenzyloxymethyl-paper and rapid hybridization by using dextran sulfate. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3683–3687. doi: 10.1073/pnas.76.8.3683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Wang C. Y., Azzo W., Al-Katib A., Chiorazzi N., Knowles D. M., 2nd Preparation and characterization of monoclonal antibodies recognizing three distinct differentiation antigens (BL1, BL2, BL3) on human B lymphocytes. J Immunol. 1984 Aug;133(2):684–691. [PubMed] [Google Scholar]
  51. Wang C. Y., Good R. A., Ammirati P., Dymbort G., Evans R. L. Identification of a p69,71 complex expressed on human T cells sharing determinants with B-type chronic lymphatic leukemic cells. J Exp Med. 1980 Jun 1;151(6):1539–1544. doi: 10.1084/jem.151.6.1539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Warnke R., Miller R., Grogan T., Pederson M., Dilley J., Levy R. Immunologic phenotype in 30 patients with diffuse large-cell lymphoma. N Engl J Med. 1980 Aug 7;303(6):293–300. doi: 10.1056/NEJM198008073030601. [DOI] [PubMed] [Google Scholar]
  53. Wong-Staal F., Reitz M. S., Jr, Gallo R. C. Retrovirus sequences in a leukemic gibbon and its contact: evidence for partial provirus in the nonleukemic gibbon. Proc Natl Acad Sci U S A. 1979 Apr;76(4):2032–2036. doi: 10.1073/pnas.76.4.2032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Wood G. S., Burke J. S., Horning S., Doggett R. S., Levy R., Warnke R. A. The immunologic and clinicopathologic heterogeneity of cutaneous lymphomas other than mycosis fungoides. Blood. 1983 Aug;62(2):464–472. [PubMed] [Google Scholar]

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