KLF13 influences multiple stages of both B and T cell development.
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.
Outram
Susan V
SV
Immunobiology Unit, Institute of Child Health, University College, London, United Kingdom. s.outram@ich.ucl.ac.uk
Gordon
Adele R
AR
Hager-Theodorides
Ariadne L
AL
Metcalfe
James
J
Crompton
Tessa
T
Kemp
Paul
P
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018956:CD5 Antigens / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D051741:Kruppel-Like Transcription Factors / Q000172:deficiency / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D017464:Receptors, Complement 3d / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000378:metabolism*
D018956:CD5 Antigens; D018797:Cell Cycle Proteins; C486422:Klf13 protein, mouse; D051741:Kruppel-Like Transcription Factors; D011948:Receptors, Antigen, T-Cell; D017464:Receptors, Complement 3d; D017455:Receptors, IgE; D012097:Repressor Proteins