ELUCIDATING REGULATORY NETWORKS PROMOTING B-CELL DEVELOPMENT

Research output: ThesisDoctoral Thesis (compilation)

Abstract

B-cells are an essential part of our adaptive immune system. A network of transcription factors together with external signals facilitate the gradual developmental progression from progenitor cells towards the B-cell fate. Several key factors participating in this network have been identified. Among these are the transcription factors E2A, HEB, EBF1 and FOXO1 as well as the IL7 signaling cascade.
The objective of this thesis has been to increase our understanding of the transcriptional network orchestrating B-lineage specification and commitment. Based on the combined expression of surface markers and transgenic reporter genes, we have identified three hierarchically related and functionally distinct subpopulations within the common lymphoid progenitor (CLP) compartment. Using this knowledge, we have re-evaluated previously characterized knock-out mouse models in order to obtain a higher resolution analysis of critical events in early B-cell commitment. Based on these studies, we propose a transcriptional hierarchy where the transcription factors E2A and HEB initiate the B-cell specification program in the LY6D- CLPs through up regulation of FOXO1. During the transition to LY6D expressing CLPs, E2A and FOXO1 induce EBF1. Subsequently, FOXO1 and EBF1 generate a feed-forward loop, leading to activation of PAX5, B-cell commitment and the progression to the CD19+ pro-B cell stage.

Details

Authors
  • Eva Welinder
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Basic Medicine
Original languageEnglish
QualificationDoctor
Awarding Institution
Supervisors/Assistant supervisor
Award date2012 Jun 1
Publisher
  • Section for Immunology, Lund University
Print ISBNs978-91-87189-08-1
Publication statusPublished - 2012
Publication categoryResearch

Bibliographic note

Defence details Date: 2012-06-01 Time: 13:00 Place: Fernström lecture hall, BMC, Lund, Sweden External reviewer(s) Name: Grosschedl, Rudolf Title: Professor Dr. Affiliation: Max Planck Institute of Immunology and Epigenetics, Freiburg, Germany ---

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Related research output

Welinder, E., Mansson, R., Mercer, E. M., David Bryder, Sigvardsson, M. & Murre, C., 2011, In : Proceedings of the National Academy of Sciences. 108, 42, p. 17402-17407

Research output: Contribution to journalArticle

Månsson, R., Zandi, S., Welinder, E., Tsapogas, P., Sakaguchi, N., David Bryder & Mikael Sigvardsson, 2010, In : Blood. 115, 13, p. 2601-2609

Research output: Contribution to journalArticle

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