Outram, SV; Gordon, AR; Hager-Theodorides, AL; Metcalfe, J; Crompton, T; Kemp, P; (2008) KLF13 influences multiple stages of both B and T cell development. CELL CYCLE , 7 (13) 2047 - 2055.
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The Kruppel-like factor, KLF13, is a member of a family of transcription factors shown to be involved in haematopoietic development. Here we show that KLF13 is involved in the development of B and T cells at multiple stages. Expression of KLF13 in the thymus was maximal in the DP population and in KLF13(-/-) deficient mice there was an accumulation of DP thymocytes and reduction of CD4(+)SP cells. Cell-surface expression of CD3(high), CD8, CD5 and HSA were altered on KLF13(-/-) DP cells, consistent with a defect in TCR signalling and at the DP to SP transition in KLF13(-/-) mice. KLF13 is also expressed in peripheral T-cells and peripheral T cell activation was impaired in KLF13(-/-) mice. Analysis of early B cell development in the bone marrow (BM) revealed a partial arrest of B cells at the transition from CD43(+) to CD43(-) pre-B cell, a transition that requires signalling through the pre-BCR. The proportion of IgM(+)/IgD(+) mature B cells was also increased in the BM of the KLF13(-/-) mice. This finding is consistent with a reduction in the strength of BCR signal or an accumulation of recirculating B cells from the periphery. Analysis of splenocytes isolated from KLF13(-/-) mice revealed an increase in the expression of CD21 and CD23 on B220(+) B cells, demonstrating a negative regulatory role for KLF13 in co-regulation of expression of CD21 and CD23. Thus KLF13 is involved at multiple different checkpoints in development that require signalling through the TCR, pre-BCR or mature BCR.
|Title:||KLF13 influences multiple stages of both B and T cell development|
|Keywords:||T-cell, B-cell, TCR, BCR, KRUPPEL-LIKE FACTOR-4, TRANSCRIPTION FACTOR, LINEAGE COMMITMENT, CD22-DEFICIENT MICE, SIGNAL-TRANSDUCTION, BONE-MARROW, IN-VIVO, ACTIVATION, THYMUS, PROLIFERATION|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Child Health > Department of Infection and Immunity > ICH - Immunobiology Unit|
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