Krüppel-like factor 4 regulates B cell number and activation-induced B cell proliferation.
Krüppel-like factor 4 (Klf4) is a transcription factor and functions in regulating cell differentiation, cell growth, and cell cycle. Although Klf4 is expressed in lymphocytes, its function in lymphocytes is unknown. In this study, we report that the levels of Klf4 expression were low in pro-B cells and continuously increased in pre-B and in mature B cells. Upon activation, Klf4 was rapidly decreased in mature B cells after 2 h of activation. A modest decrease in numbers of pre-B cells in bone marrow and mature B cells in spleen was observed in Klf4-deficient mice. In the absence of Klf4, fewer B cells entered the S phase of the cell cycle and completed cell division in response to the engagement of BCR and/or CD40 in vitro. Furthermore, the delay in entering the cell cycle is associated with decreased expression of cyclin D2 in B cells that lack Klf4 expression. We then demonstrated that Klf4 directly bound to the promoter of cyclin D2 and regulated its expression. These findings demonstrate that Klf4 regulates B cell number and activation-induced B cell proliferation through directly acting on the promoter of cyclin D2.
Klaewsongkram
Jettanong
J
Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Yang
Yinhua
Y
Golech
Susanne
S
Katz
Jonathan
J
Kaestner
Klaus H
KH
Weng
Nan-Ping
NP
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D056742:Cyclin D2; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism
C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D016213:Cyclins; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors