PMID- 17878366 OWN - NLM STAT- MEDLINE DCOM- 20071106 LR - 20220330 IS - 0022-1767 (Print) IS - 1550-6606 (Electronic) IS - 0022-1767 (Linking) VI - 179 IP - 7 DP - 2007 Oct 1 TI - Kruppel-like factor 4 regulates B cell number and activation-induced B cell proliferation. PG - 4679-84 AB - Kruppel-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. FAU - Klaewsongkram, Jettanong AU - Klaewsongkram J AD - Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. FAU - Yang, Yinhua AU - Yang Y FAU - Golech, Susanne AU - Golech S FAU - Katz, Jonathan AU - Katz J FAU - Kaestner, Klaus H AU - Kaestner KH FAU - Weng, Nan-Ping AU - Weng NP LA - eng GR - Z01 AG000757-10/Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Ccnd2 protein, mouse) RN - 0 (Cyclin D2) RN - 0 (Cyclins) RN - 0 (Klf4 protein, mouse) RN - 0 (Kruppel-Like Factor 4) RN - 0 (Kruppel-Like Transcription Factors) SB - IM MH - Animals MH - B-Lymphocytes/*cytology/*immunology/metabolism MH - Bone Marrow Cells/cytology/immunology/metabolism MH - Cell Differentiation MH - Cell Proliferation MH - Cells, Cultured MH - Cyclin D2 MH - Cyclins/genetics/metabolism MH - Gene Expression Regulation MH - Kruppel-Like Factor 4 MH - Kruppel-Like Transcription Factors/deficiency/genetics/*metabolism MH - Lymphocyte Activation/*immunology MH - Mice MH - Mice, Knockout MH - Promoter Regions, Genetic/genetics MH - Protein Binding MH - Spleen/cytology/immunology/metabolism PMC - PMC2262926 MID - NIHMS41126 COIS- Disclosures The authors have no financial conflict of interest. EDAT- 2007/09/20 09:00 MHDA- 2007/11/07 09:00 PMCR- 2008/03/05 CRDT- 2007/09/20 09:00 PHST- 2007/09/20 09:00 [pubmed] PHST- 2007/11/07 09:00 [medline] PHST- 2007/09/20 09:00 [entrez] PHST- 2008/03/05 00:00 [pmc-release] AID - 179/7/4679 [pii] AID - 10.4049/jimmunol.179.7.4679 [doi] PST - ppublish SO - J Immunol. 2007 Oct 1;179(7):4679-84. doi: 10.4049/jimmunol.179.7.4679.