umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
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.
Umeå University, Faculty of Medicine, Medical Biosciences, Medical and Clinical Genetics.
Umeå University, Faculty of Medicine, Medical Biosciences, Medical and Clinical Genetics.
Umeå University, Faculty of Medicine, Medical Biosciences, Medical and Clinical Genetics.
Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
2006 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 43, no 9, 1316-1324 p.Article in journal (Refereed) Published
Abstract [en]

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.
Keyword [en]
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
Identifiers
URN: urn:nbn:se:umu:diva-15302DOI: 10.1016/j.molimm.2005.09.020PubMedID: 16321440OAI: oai:DiVA.org:umu-15302DiVA: diva2:154974
Available from: 2008-01-11 Created: 2008-01-11 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Molecular genetics of B- and T-lymphocyte development
Open this publication in new window or tab >>Molecular genetics of B- and T-lymphocyte development
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Lymphocytes are essential for the generation of specific immunity. Development of B cells in the bone marrow and T cells in the thymus have several analogous features, and are tightly regulated processes. Even though there is an increasing amount of information concerning lymphopoiesis, a lot of questions remain. The aim of this thesis has been to understand some of the molecular events that contribute to the control of lymphocyte development.

Expression of the B cell receptor is an important checkpoint in B lymphocyte development. The Dµ protein is a truncated B cell receptor that can induce some of the signals elicited by full length µ, but cannot promote further B cell differentiation. In order to determine if this could stem from an impaired survival signal, we introduced Bcl-2 into RAG2 deficient Dµ transgenic mice. Analysis of these mice showed that Dµ could not support pre-B cell maturation despite extended survival of B cell precursors by Bcl-2. In addition, data from recombination competent Dµ transgenic mice demonstrated that the Dµ induced partial block is permissive for marginal zone B cell development, whereas the formation of follicular B cells is severely reduced.

The bHLH family of transcription factors is known to be involved in the regulation of lymphocyte development. Whereas the roles of E2A and HEB have been well documented in both B- and T-lymphocytes, detailed knowledge concerning E2-2 is lacking. To address the role of E2-2 in B cell development, we have reconstituted mice, using E2-2 deficient fetal liver cells, and analysed the B cell compartments. We also measured mRNA expression patterns for the three E-proteins in wildtype mice. Resulting data show that, in addition to a role in B cell lineage entry, E2-2 is required for efficient expansion of pro-B cells, and also influences the follicular versus marginal zone decision.

While focusing on assigning a role for E2-2 in T-cell development, we analyzed the expression of the E-proteins during this process and performed functional studies in fetal thymic organ cultures. E2-2 deficient mouse embryos were shown to display a partial block at the DN3 stage, which was not due to proliferation or apoptosis defects. In addition, analysis of expression levels of the pre-Talpha chain suggests that E2-2 may play a role in the regulation of transcription of pre-Talpha, and therefore in the assembly of the pre-T cell receptor.

Place, publisher, year, edition, pages
Umeå: Medicinsk biovetenskap, 2006. 72 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1030
Keyword
lymphocyte development, Dmu protein, transcription factor, bHLH, E2-2, T cell, B cell, marginal zone
National Category
Medical Genetics
Identifiers
urn:nbn:se:umu:diva-802 (URN)91-7264-089-8 (ISBN)
Public defence
2006-06-09, Betula, 6M, Norrlands Universitetssjukhus (NUS), Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2006-05-15 Created: 2006-05-15 Last updated: 2009-10-30Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=16321440&dopt=Citation

Search in DiVA

By author/editor
Holmberg, Dan
By organisation
Medical and Clinical GeneticsPathology
In the same journal
Molecular Immunology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 34 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf