Enforced expression of the transcriptional coactivator OBF1 impairs B cell differentiation at the earliest stage of development

Alain Bordon, Nabil Bosco, Camille Du Roure, Boris A. Bartholdy, Hubertus Kohler, Gabriele Matthias, Antonius G. Rolink, Patrick Matthias

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

OBF1, also known as Bob.1 or OCA-B, is a B lymphocyte-specific transcription factor which coactivates Oct1 and Oct2 on B cell specific promoters. So far, the function of OBF1 has been mainly identified in late stage B cell populations. The central defect of OBF1 deficient mice is a severely reduced immune response to T cell-dependent antigens and a lack of germinal center formation in the spleen. Relatively little is known about a potential function of OBF1 in developing B cells. Here we have generated transgenic mice overexpressing OBF1 in B cells under the control of the immunoglobulin heavy chain promoter and enhancer. Surprisingly, these mice have greatly reduced numbers of follicular B cells in the periphery and have a compromised immune response. Furthermore, B cell differentiation is impaired at an early stage in the bone marrow: a first block is observed during B cell commitment and a second differentiation block is seen at the large preB2 cell stage. The cells that succeed to escape the block and to differentiate into mature B cells have post-translationally downregulated the expression of transgene, indicating that expression of OBF1 beyond the normal level early in B cell development is deleterious. Transcriptome analysis identified genes deregulated in these mice and Id2 and Id3, two known negative regulators of B cell differentiation, were found to be upregulated in the EPLM and preB cells of the transgenic mice. Furthermore, the Id2 and Id3 promoters contain octamer-like sites, to which OBF1 can bind. These results provide evidence that tight regulation of OBF1 expression in early B cells is essential to allow efficient B lymphocyte differentiation.

Original languageEnglish (US)
Article numbere4007
JournalPLoS One
Volume3
Issue number12
DOIs
StatePublished - Dec 23 2008
Externally publishedYes

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cell differentiation
B-lymphocytes
Cell Differentiation
B-Lymphocytes
Cells
mice
Lymphocytes
promoter regions
Transgenic Mice
immune response
genetically modified organisms
immunoglobulin heavy chains
Immunoglobulin Heavy Chains
T-cells
Germinal Center
Gene Expression Profiling
cells
transcriptomics
Transgenes
bone marrow

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Enforced expression of the transcriptional coactivator OBF1 impairs B cell differentiation at the earliest stage of development. / Bordon, Alain; Bosco, Nabil; Du Roure, Camille; Bartholdy, Boris A.; Kohler, Hubertus; Matthias, Gabriele; Rolink, Antonius G.; Matthias, Patrick.

In: PLoS One, Vol. 3, No. 12, e4007, 23.12.2008.

Research output: Contribution to journalArticle

Bordon, Alain ; Bosco, Nabil ; Du Roure, Camille ; Bartholdy, Boris A. ; Kohler, Hubertus ; Matthias, Gabriele ; Rolink, Antonius G. ; Matthias, Patrick. / Enforced expression of the transcriptional coactivator OBF1 impairs B cell differentiation at the earliest stage of development. In: PLoS One. 2008 ; Vol. 3, No. 12.
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