title: Krüppel-like factor 2 (KLF2) regulates B-cell reactivity, subset differentiation, and trafficking molecule expression.
abstract: The transcription factor Krüppel-like factor 2 (KLF2) is critical for normal trafficking of T lymphocytes, but its role in B cells is unclear. We report that B cell-specific KLF2 deficiency leads to decreased expression of the trafficking molecules CD62L and β7-integrin, yet expression of sphingosine-1 phosphate receptor 1 (which is a critical target of KLF2 in T cells) was, unexpectedly, minimally altered. Unexpectedly, Klf2 deletion led to a drastic reduction in the B1 B-cell pool and a substantial increase in transitional and marginal zone B-cell numbers. In addition, we observed that KLF2-deficient B cells showed increased apoptosis and impaired proliferation after B-cell receptor cross-linking. Gene expression analysis indicated that KLF2-deficient follicular B cells display numerous characteristics shared by normal marginal zone B cells, including reduced expression of several signaling molecules that may contribute to defective activation of these cells. Hence, our data indicate that KLF2 plays a critical role in dictating normal subset differentiation and functional reactivity of mature B cells.
authors.affiliation: Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN 55414, USA.
authors.forename: Geoffrey T
authors.initials: GT
authors.lastname: Hart
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Wang
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Hogquist
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Jameson
mesh_terms: D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D002454:Cell Differentiation; D002460:Cell Line; D005434:Flow Cytometry / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence / Q000379:methods; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D014018:Tissue Distribution
chemical_list: C096161:KLF2 protein, human; C498314:Klf2 protein, mouse; D051741:Kruppel-Like Transcription Factors