Impaired T- and B-cell development in Tcl1-deficient mice.
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.
University of Alabama at Birmingham and the Howard Hughes Medical Institute, USA.
Sang-Moo
SM
Kang
Maria Grazia
MG
Narducci
Cristina
C
Lazzeri
Adriana M
AM
Mongiovì
Elisabetta
E
Caprini
Antonella
A
Bresin
Fabio
F
Martelli
Jay
J
Rothstein
Carlo Maria
CM
Croce
Max D
MD
Cooper
Giandomenico
G
Russo
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D002470:Cell Survival; D017931:DNA Primers; D051379:Mice; D018345:Mice, Knockout; D005810:Multigene Family; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic
D017931:DNA Primers; D011518:Proto-Oncogene Proteins; C490393:Tcl1 protein, mouse