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Research Article Free access | 10.1172/JCI118978

Requirement for increased IL-10 in the development of B-1 lymphoproliferative disease in a murine model of CLL.

S Ramachandra, R A Metcalf, T Fredrickson, G E Marti, and E Raveche

Department of Pathology, University of Medicine and Dentistry of New Jersey, Newark 07103, USA.

Find articles by Ramachandra, S. in: PubMed | Google Scholar

Department of Pathology, University of Medicine and Dentistry of New Jersey, Newark 07103, USA.

Find articles by Metcalf, R. in: PubMed | Google Scholar

Department of Pathology, University of Medicine and Dentistry of New Jersey, Newark 07103, USA.

Find articles by Fredrickson, T. in: PubMed | Google Scholar

Department of Pathology, University of Medicine and Dentistry of New Jersey, Newark 07103, USA.

Find articles by Marti, G. in: PubMed | Google Scholar

Department of Pathology, University of Medicine and Dentistry of New Jersey, Newark 07103, USA.

Find articles by Raveche, E. in: PubMed | Google Scholar

Published October 15, 1996 - More info

Published in Volume 98, Issue 8 on October 15, 1996
J Clin Invest. 1996;98(8):1788–1793. https://doi.org/10.1172/JCI118978.
© 1996 The American Society for Clinical Investigation
Published October 15, 1996 - Version history
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Abstract

Malignant B-1 cells derived from NZB mice, a murine model of spontaneous autoimmunity and B cell lymphoproliferative disease, produce significantly higher levels of IL-10 mRNA than normal B-1 or B cells. IL-10 may act as an autocrine growth factor for the expansion of malignant B-1 cells. In order to determine if elevated endogenous production of IL-10 was a required element for the malignant transformation of B-1 cells in NZB mice, backcross animals were studied for the linkage between elevated IL-10 expression and the presence of lymphoid malignancy. The phenotypes of aged (NZB x DBA/2)F1 x NZB animals were determined and a strong correlation was found between the elevated levels of IL-10 mRNA and the development of B-1 malignant clones. In contrast, an increased level of IL-10 message was not associated with elevated serum IgM or the presence of anemia or reticulocytosis which is mainly seen in response to autoantibody production. These results indicate that, at least in NZB, the autoimmunity and lymphoproliferation phenotypes are not linked genetically. IL-10 may enhance proliferation and the development of B-1 cell malignancy rather than antibody production by the B-1 cell subpopulation. Thus, IL-10 plays an important role in B-1 malignancies, and downregulation of IL-10 could be a likely site for intervention in B cell malignancies.

Version history
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