title: B cell homeostasis and plasma cell homing controlled by Krüppel-like factor 2.
abstract: Krüppel-like factor 2 (KLF2) controls T lymphocyte egress from lymphoid organs by regulating sphingosin-1 phosphate receptor 1 (S1Pr1). Here we show that this is not the case for B cells. Instead, KLF2 controls homeostasis of B cells in peripheral lymphatic organs and homing of plasma cells to the bone marrow, presumably by controlling the expression of β(7)-integrin. In mice with a B cell-specific deletion of KLF2, S1Pr1 expression on B cells was only slightly affected. Accordingly, all splenic B cell subsets including B1 cells were present, but their numbers were increased with a clear bias for marginal zone (MZ) B cells. In contrast, fewer peyers patches harboring fewer B cells were found, and fewer B1 cells in the peritoneal cavity as well as recirculating B cells in the bone marrow were detected. Upon thymus-dependent immunization, IgG titers were diminished, and antigen-specific plasma cells were absent in the bone marrow, although numbers of antigen-specific splenic plasmablasts were normal. KLF2 plays also a role in determining the identity of follicular B cells, as KLF2-deficient follicular B cells showed calcium responses similar to those of MZ B cells and failed to down-regulate MZ B cell signature genes, such as CD21 and CXCR7.
authors.affiliation: Division of Molecular Immunology, Nikolaus-Fiebiger-Center, Department of Internal Medicine III, Friedrich-Alexander-University Erlangen-Nürnberg, D-91054 Erlangen, Germany.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Winkelmann
authors.forename: Lena
authors.initials: L
authors.lastname: Sandrock
authors.forename: Martina
authors.initials: M
authors.lastname: Porstner
authors.forename: Edith
authors.initials: E
authors.lastname: Roth
authors.forename: Martina
authors.initials: M
authors.lastname: Mathews
authors.forename: Elias
authors.initials: E
authors.lastname: Hobeika
authors.forename: Michael
authors.initials: M
authors.lastname: Reth
authors.forename: Mark L
authors.initials: ML
authors.lastname: Kahn
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schuh
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Jäck
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D001854:Bone Marrow Cells / Q000166:cytology; D002118:Calcium / Q000378:metabolism; D000068876:Fingolimod Hydrochloride; D017353:Gene Deletion; D039641:Integrin beta Chains / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D019041:L-Selectin / Q000096:biosynthesis; D051917:Leukosialin / Q000096:biosynthesis; D051379:Mice; D008954:Models, Biological; D010950:Plasma Cells / Q000166:cytology*; D011409:Propylene Glycols / Q000494:pharmacology; D017455:Receptors, IgE / Q000096:biosynthesis; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D039641:Integrin beta Chains; C498314:Klf2 protein, mouse; D051741:Kruppel-Like Transcription Factors; D051917:Leukosialin; D011409:Propylene Glycols; D017455:Receptors, IgE; D049349:Receptors, Lysosphingolipid; C091368:integrin beta7; D019041:L-Selectin; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine; D002118:Calcium