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Updated: May 8, 2026

Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells
Published on: February 21, 2018
Inducible expression of hyperactive Syk in B cells activates Blimp-1-dependent terminal differentiation
11] BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-Universität, Freiburg, Germany [2] Department of Molecular Immunology, Faculty of Biology, Albert-Ludwigs-Universität, Freiburg, Germany [3] Max-Planck-Institute of Immunobiology and Epigenetics, Freiburg, Germany.
Abstract:
The non-receptor protein tyrosine kinase Syk (spleen tyrosine kinase) is an important mediator of signal transduction in B cells. By acting downstream of the B-cell antigen receptor, Syk promotes signaling pathways involved in proliferation, differentiation and survival of B cells. To study the oncogenic potential of Syk, we generated a mouse model for the inducible expression of the leukemia-derived TEL-Syk fusion protein exhibiting constitutive kinase activity. To achieve B-cell-specific expression of TEL-Syk in adult mice, we used a tamoxifen-inducible Cre mouse line. This study shows that inducible expression of TEL-Syk in B cells leads to transient proliferation and subsequent plasma cell differentiation. However, it does not lead to B-cell transformation. Instead, Syk activation induces the tumor suppressor B-lymphocyte-induced maturation protein-1 (Blimp-1), which interferes with the expression of the antiapoptotic protein Bcl-2. Combined induction of TEL-Syk with transgenic expression of Bcl-2 results in a severe phenotype and plasma cell expansion. Our results suggest that deregulated Syk activity by itself is not sufficient for the transformation of B cells, as downstream effectors, such as Blimp-1, limit the survival and expansion of the activated B cell.
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