Transgenic expression of VpreB-3 under the control of the immunoglobulin heavy chain enhancer and SV40 promoter.

Recently we isolated a novel gene, VpreB-3 gene from the cDNA library of a pre-B cell clone. This gene is selectively expressed in pre-B and bone marrow-derived B cell lines. Its products are associated with the immunoglobulin heavy (IgH) chain in pre-B cell line. In the present study, to address the role of VpreB-3 on B cell development, transgenic mice carrying the VpreB-3 gene under the control of the IgH enhancer and SV40 promoter were produced. The transgenic mice expressed the VpreB-3 gene in bone marrow and spleen at a high level compared with control mice. In the thymus, the expression of the transgene was also detected, although its level was low. Flow cytometry analysis revealed that the frequency of CD45R+ and mu+ B cells were reduced in the bone marrow of 2 of the 11 transgenic mice and also reduced in the spleen of 1 of the transgenic mice. Furthermore, the results of a stromal cell-dependent B cell culture assay suggested that early B cell development, the differentiation from CD45R- B progenitor cells to CD45R+ pro-B cells, was delayed in the bone marrow cultures of 3 of the 5 transgenic mice compared with the control mice. These results suggested that VpreB-3 products may play some role in early B cell development at the stage of CD45R- B progenitor cells before the expression of surface mu chains.