KLF13 influences multiple stages of both B and T cell development

Abstract

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 CD3high, 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.