3' enhancers hs3b/hs4 are dispensable for deregulation in mouse plasmacytomas with T(12;15) translocations.

-deregulating T(12;15) chromosomal translocations are the hallmark cytogenetic abnormalities of murine plasmacytomas (PCTs). In most PCTs, the immunoglobulin heavy chain () locus is broken between the enhancer and the 3' regulatory region (), making the latter the major candidate for orchestrating deregulation. To elucidate the role of the in tumorigenesis, we induced PCTs in transgenic mice deficient for the major enhancer elements, and (hs3b-4).

Transgenes of the mouse immunoglobulin heavy chain locus, lacking distal elements in the 3' regulatory region, are impaired for class switch recombination.

The immunoglobulin heavy (H) chain class switch is mediated by a deletional recombination event between µ and γ, α, or ε constant region genes. This recombination event is upregulated during immune responses by a regulatory region that lies 3' of the constant region genes. We study switch recombination using a transgene of the entire murine H chain constant region locus.

Oncogenic Myc translocations are independent of chromosomal location and orientation of the immunoglobulin heavy chain locus.

Many tumors are characterized by recurrent translocations between a tissue-specific gene and a proto-oncogene. The juxtaposition of the Ig heavy chain gene and Myc in Burkitt's lymphoma and in murine plasmacytoma is a classic example. Regulatory elements within the heavy chain constant region locus are required for Myc translocation and/or deregulation.

Enhancement of antibody class-switch recombination by the cumulative activity of four separate elements.

Class-switch recombination of Ab isotype is mediated by a recombinational DNA deletion event and must be robustly upregulated during Ag-driven differentiation of B cells. The enhancer region 3' of the Cα gene is important for the upregulation of switch recombination. Using a transgene of the entire H chain C region locus, we demonstrate in this study that it is the four 3' enhancer elements themselves (a total of 4.

Excessive amounts of mu heavy chain block B-cell development.

Antigen-independent B-cell development occurs in several stages that depend on the expression of Ig heavy and light chain. We identified a line of mice that lacked mature B cells in the spleen. This mouse line carried approximately 11 copies of a transgene of the murine heavy chain constant region locus, and B-lineage cells expressed excessive amounts of the intracellular μ heavy chain.