Dmu expression causes enrichment of MZ B cells, but is non permissive for B cell maturation in Rag2-/- mice even if combined with Bcl-2.
2006 (English)In: Molecular Immunology, ISSN 0161-5890, Vol. 43, no 9, 1316-1324 p.Article in journal (Refereed) Published
Rearrangements in reading frame 2 promote the expression of a truncated heavy chain, the Dmu protein. Dmu can assemble into a pre-B cell receptor like complex that appears to induce a subset of signals elicited by full length mu, but cannot promote the pro-B to pre-B cell transition of Rag-/- B cells. In order to determine if this could stem from an impaired survival signal not properly induced by the Dmu protein, we introduced Bcl-2 into Dmu-transgenic, Rag2-/- mice. Despite the fact that the Bcl-2 transgene expression promoted some increase in the fraction of CD43- B cells, an identical increase was also observed in Rag2-/- mice. Moreover, whereas in mu-transgenic Rag2-/-Bcl-2+ mice, CD2 and CD25 expression were up regulated and c-Kit was down regulated, these markers were unaltered in Dmu-transgenic Rag2-/- Bcl-2+ mice compared to Rag2-/- Bcl-2+ mice, indicating that Dmu cannot support pre-B cell maturation despite extended survival of B cell precursors by Bcl-2. In addition, we observed that in Dmu-transgenic recombination competent mice, the Dmu induced partial block is permissive for marginal zone B cell development whereas the formation of follicular B cells is severely reduced. While the Dmu protein is expressed in peripheral B cells escaping the block, only a minor fraction of Dmu is exposed to the outer cell surface.
Place, publisher, year, edition, pages
2006. Vol. 43, no 9, 1316-1324 p.
Animals, B-Lymphocytes/*cytology/*immunology, Base Sequence, Cell Differentiation, DNA/genetics, DNA-Binding Proteins/*deficiency/genetics, Gene Expression, Gene Rearrangement; B-Lymphocyte; Heavy Chain, Genes; bcl-2, Humans, Immunoglobulin mu-Chains/*genetics, Mice, Mice; Knockout, Mice; Transgenic
IdentifiersURN: urn:nbn:se:umu:diva-15302DOI: 10.1016/j.molimm.2005.09.020PubMedID: 16321440OAI: oai:DiVA.org:umu-15302DiVA: diva2:154974