Transgenic mice carrying the human T-cell lymphotopic virus (HTLV)-I-tax gene develop several abnormalities, including the appearance of neurofibromas and an exocrinopathy which shares some similarity to human Sjoegren's syndrome. The HTLV-I-tax transgenic mice manifest a marked lymphadenopathy and marked elevation of serum immunoglobulin levels which is reminiscent of the progressive lymphoproliferative disorders which are seen in patient's with human Sjoegren's syndrome, who may occasionally develop overt lymphomas. Previous work using these transgenic animals has demonstrated that the expression of the tax gene alters the normal regulation of several growth factors and receptors which may be involved in the tax-induced transformation process. The focus of the current work is to determine the mechanism by which tax may lead to the marked B-cell lymphoid hyperplasia and elevated serum immunoglobulin levels observed in these transgenic animals. Studies are continuing to attempt to isolate and clone a B-cell growth factor (BCGF) which may be responsible for this phenomenon of B-cell proliferation as well as a B-cell differentiation factor responsible for stimulating IgM secretion (BCDF). This work may provide novel insights into B-cell proliferation with implications for further mechanisms of tax action as well as further understanding of factors which may be involved in the lymphoproliferative disorder of Sjoegren's syndrome.
