Impaired T- and B-cell development in Tcl1-deficient mice

Blood. 2005 Feb 1;105(3):1288-94. doi: 10.1182/blood-2004-04-1453. Epub 2004 Oct 12.

Abstract

TCL1, the overexpression of which may result in T-cell leukemia, is normally expressed in early embryonic tissues, the ovary, and lymphoid lineage cells. Our analysis of mouse B-lineage cells indicates that Tcl1 expression is initiated in pro-B cells and persists in splenic marginal zone and follicular B cells. T-lineage Tcl1 expression begins in thymocyte progenitors, continues in CD4(+)CD8(+) thymocytes, and is extinguished in mature T cells. In Tcl1-deficient mice, we found B lymphopoiesis to be compromised at the pre-B cell stage and T-cell lymphopoiesis to be impaired at the CD4(+)CD8(+) thymocyte stage. A corresponding increase was observed in thymocyte susceptibility to anti-CD3epsilon-induced apoptosis. Reduced numbers of splenic follicular and germinal center B cells were accompanied by impaired production of immunoglobulin G1 (IgG1) and IgG2b antibodies in response to a T-dependent antigen. The marginal zone B cells and T-cell-independent antibody responses were also diminished in Tcl1(-/-) mice. This analysis indicates a significant role for Tcl1, a coactivator of Akt signaling, in normal T- and B-cell development and function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibody Formation
  • B-Lymphocytes / immunology*
  • Cell Division
  • Cell Survival
  • DNA Primers
  • Mice
  • Mice, Knockout
  • Multigene Family
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins / deficiency*
  • Proto-Oncogene Proteins / genetics*
  • T-Lymphocytes / immunology*
  • Transcription, Genetic*

Substances

  • DNA Primers
  • Proto-Oncogene Proteins
  • Tcl1 protein, mouse