Characteristics of a spontaneous monoclonal thymocytotoxic antibody from New Zealand black mice

Recognition of a specific NTA determinant

K. R. Bray, M. Eric Gershwin, T. Chused, A. Ahmed

Research output: Contribution to journalArticle

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Abstract

Naturally occurring thymocytotoxic autoantibodies (NTA) have been described both in humans and in mice with SLE, and have been reported to be preferentially reactive with T suppressor as compared to T helper cells. However, although NTA has been shown by some groups of investigators to induce autoantibodies in normal strains of mice, other researchers have suggested that NTA has only a minor, if any, role in murine lupus. We have been studying the characteristics of a monoclonal antibody (TC-17) derived from the fusion of 4-mo-old NZB spleen cells with P3-X63-AG8.653 plasmacytoma cells. This monoclonal IgM reagent is cytotoxic for approximately 40% of total thymocytes, 50% of cortical thymocytes, less than 1% of cortisol-resistant thymocytes, 10% of splenocytes and lymph node cells, and less than 3% of bone marrow and fetal liver cells. The thymocytotoxicity can be absorbed by thymocytes but not by brain cells. Although NZB, NZW, NFS, and BALB/c thymocytes all manifest reactivity with TC-17, there was considerable difference between strains with respect to antigen density; NZB thymocytes have the highest density. By FACS analysis, TC-17 occurs independently of Lyt-1, Lyt-2, and T helper cell-specific antigens, and is more prevalent on larger proliferating thymocytes. TC-17 augments the response to SRBC but does not influence responses to TI-1 (TNP-BA) or TI-2 (DNP-Ficoll) antigen and production of LPS-induced B cell colonies. We believe that TC-17 recognizes a new T cell antigen, probably one involved in T cell differentiation. Because this monoclonal NTA reacts with only 40% of thymocytes, and is not absorbed with brain, it would not have been detected in mouse sera by using previously published methods. NTA are a heterogeneous group of autoantibodies; some specificities such as TC-17 went unrecognized in the past, and may be important either for disease pathogenesis or for secondary immunologic abnormalities.

Original languageEnglish (US)
Pages (from-to)1318-1324
Number of pages7
JournalJournal of Immunology
Volume133
Issue number3
StatePublished - 1984

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Thymocytes
New Zealand
Autoantibodies
Monoclonal Antibodies
Antigens
Research Personnel
T-Lymphocytes
Th2 Cells
Plasmacytoma
Viral Tumor Antigens
Brain
Helper-Inducer T-Lymphocytes
Immunoglobulin M
Hydrocortisone
Cell Differentiation
B-Lymphocytes
Spleen
Lymph Nodes
Bone Marrow
Liver

ASJC Scopus subject areas

  • Immunology

Cite this

Characteristics of a spontaneous monoclonal thymocytotoxic antibody from New Zealand black mice : Recognition of a specific NTA determinant. / Bray, K. R.; Gershwin, M. Eric; Chused, T.; Ahmed, A.

In: Journal of Immunology, Vol. 133, No. 3, 1984, p. 1318-1324.

Research output: Contribution to journalArticle

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abstract = "Naturally occurring thymocytotoxic autoantibodies (NTA) have been described both in humans and in mice with SLE, and have been reported to be preferentially reactive with T suppressor as compared to T helper cells. However, although NTA has been shown by some groups of investigators to induce autoantibodies in normal strains of mice, other researchers have suggested that NTA has only a minor, if any, role in murine lupus. We have been studying the characteristics of a monoclonal antibody (TC-17) derived from the fusion of 4-mo-old NZB spleen cells with P3-X63-AG8.653 plasmacytoma cells. This monoclonal IgM reagent is cytotoxic for approximately 40{\%} of total thymocytes, 50{\%} of cortical thymocytes, less than 1{\%} of cortisol-resistant thymocytes, 10{\%} of splenocytes and lymph node cells, and less than 3{\%} of bone marrow and fetal liver cells. The thymocytotoxicity can be absorbed by thymocytes but not by brain cells. Although NZB, NZW, NFS, and BALB/c thymocytes all manifest reactivity with TC-17, there was considerable difference between strains with respect to antigen density; NZB thymocytes have the highest density. By FACS analysis, TC-17 occurs independently of Lyt-1, Lyt-2, and T helper cell-specific antigens, and is more prevalent on larger proliferating thymocytes. TC-17 augments the response to SRBC but does not influence responses to TI-1 (TNP-BA) or TI-2 (DNP-Ficoll) antigen and production of LPS-induced B cell colonies. We believe that TC-17 recognizes a new T cell antigen, probably one involved in T cell differentiation. Because this monoclonal NTA reacts with only 40{\%} of thymocytes, and is not absorbed with brain, it would not have been detected in mouse sera by using previously published methods. NTA are a heterogeneous group of autoantibodies; some specificities such as TC-17 went unrecognized in the past, and may be important either for disease pathogenesis or for secondary immunologic abnormalities.",
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