Conversion of mature B cells into T cells by dedifferentiation to uncommitted progenitors

Nature. 2007 Sep 27;449(7161):473-7. doi: 10.1038/nature06159. Epub 2007 Sep 12.

Abstract

Lineage commitment and differentiation to a mature cell type are considered to be unidirectional and irreversible processes under physiological conditions. The commitment of haematopoietic progenitors to the B-cell lineage and their development to mature B lymphocytes critically depend on the transcription factor encoded by the paired box gene 5 (Pax5). Here we show that conditional Pax5 deletion in mice allowed mature B cells from peripheral lymphoid organs to dedifferentiate in vivo back to early uncommitted progenitors in the bone marrow, which rescued T lymphopoiesis in the thymus of T-cell-deficient mice. These B-cell-derived T lymphocytes carried not only immunoglobulin heavy- and light-chain gene rearrangements but also participated as functional T cells in immune reactions. Mice lacking Pax5 in mature B cells also developed aggressive lymphomas, which were identified by their gene expression profile as progenitor cell tumours. Hence, the complete loss of Pax5 in late B cells could initiate lymphoma development and uncovered an extraordinary plasticity of mature peripheral B cells despite their advanced differentiation stage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology*
  • Cell Differentiation*
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • Gene Deletion
  • Gene Rearrangement, B-Lymphocyte / genetics
  • Immunoglobulins / genetics
  • Immunoglobulins / immunology
  • Lymphoma / genetics
  • Lymphoma / pathology
  • Mice
  • Mice, Inbred C57BL
  • PAX5 Transcription Factor / deficiency
  • PAX5 Transcription Factor / genetics
  • Stem Cells / cytology*
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • Thymus Gland / cytology
  • Thymus Gland / metabolism

Substances

  • DNA-Binding Proteins
  • Immunoglobulins
  • PAX5 Transcription Factor
  • Pax5 protein, mouse
  • Rag2 protein, mouse

Associated data

  • GEO/GSM210098
  • GEO/GSM210099
  • GEO/GSM210100
  • GEO/GSM210101
  • GEO/GSM213736
  • GEO/GSM215734
  • GEO/GSM215735