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Abnormal B-cell function in HTLV-I-tax transgenic mice
R S Peebles1, C R Maliszewski, T A Sato
1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224.
Oncogene
|March 16, 1995
Summary
Transgenic mice with the HTLV-I Tax gene exhibit B-cell abnormalities. Their cell cultures produce factors that promote B-cell growth and immunoglobulin secretion, suggesting novel autoimmune disease pathways.
Area of Science:
- Immunology
- Molecular Biology
- Pathology
Background:
- Transgenic mice expressing the HTLV-I Tax gene develop exocrinopathy resembling Sjoegren's syndrome.
- These mice display B-lymphocyte-predominant lymphadenopathy and splenomegaly with altered immunoglobulin levels.
Purpose of the Study:
- To investigate if the Human T-lymphotropic virus type I (HTLV-I) Tax gene induces cytokines, leading to lymphadenopathy in transgenic mice.
- To explore the in vitro B-cell responses to factors produced by cell lines derived from these mice.
Main Methods:
- Utilized cell lines from HTLV-I Tax transgenic mice.
- Assessed B-cell proliferation and immunoglobulin (IgM) secretion in response to conditioned media (CM).
- Investigated the role of supplemental cytokines in conjunction with CM.
Main Results:
- Conditioned media from the transgenic mouse cell lines induced B-cell proliferation when combined with surface Ig cross-linking.
- CM significantly enhanced IgM secretion by spleen cells and purified B-cells.
- The observed B-cell responses were not attributable to any known cytokine, suggesting novel factors.
Conclusions:
- Conditioned media from HTLV-I Tax transgenic mouse cell lines contain previously unidentified factors.
- These factors mediate novel pathways of B-cell growth and differentiation.
- These novel pathways may contribute to the pathological development of autoimmune diseases.