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Transforming growth factor type beta (TGF beta) inhibits G1 to S transition, but not activation of human B
Abstract:
Type beta transforming growth factor (TGF beta) is a polypeptide that may influence the growth of a variety of cell types in a positive or negative fashion. In this study we show that TGF beta markedly inhibits DNA synthesis in normal and neoplastic human B lymphocytes stimulated to proliferate with anti-immunoglobulins and B-cell growth factor (BCGF). Although TGF beta was needed during the initial 12 h of the culture to promote optimal inhibition, we found that it had little or no effect on several early to intermediate parameters of cell activation [( Ca2+]i increase, c-myc mRNA increase, cellular enlargement, RNA increase, and the increase in the expression of the 4F2 activation antigen). In contrast, TGF beta almost completely blocked the induction of transferrin receptor expression, which normally occurs in the late G1 phase of the cell cycle. Therefore, we conclude that TGF beta treatment leads to arrest of the cells in the middle to late G1 phase, prior to transferrin receptor expression.
Insights
Type beta transforming growth factor (TGF beta) inhibits DNA synthesis in human B lymphocytes. This immune cell growth factor arrests cells in the G1 phase before transferrin receptor expression.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Type beta transforming growth factor (TGF beta) is a polypeptide influencing cell growth.
- B lymphocytes play a crucial role in the adaptive immune response.
Purpose of the Study:
- To investigate the effect of TGF beta on human B lymphocyte proliferation.
- To determine the specific cell cycle phase affected by TGF beta.
Main Methods:
- Normal and neoplastic human B lymphocytes were stimulated to proliferate.
- Cells were treated with TGF beta and analyzed for DNA synthesis and cell cycle parameters.
- Key activation markers and gene expression were monitored.
Main Results:
- TGF beta markedly inhibited DNA synthesis in stimulated B lymphocytes.
- TGF beta did not significantly affect early to intermediate cell activation markers.
- TGF beta blocked the induction of transferrin receptor expression, a late G1 event.
Conclusions:
- TGF beta arrests human B lymphocytes in the middle to late G1 phase of the cell cycle.
- The mechanism involves preventing progression to transferrin receptor expression.
- TGF beta's inhibitory effect on B cell proliferation is cell cycle-specific.