title: Follicular B cell trafficking within the spleen actively restricts humoral immune responses.
abstract: Follicular (FO) and marginal zone (MZ) B cells are maintained in distinct locations within the spleen, but the genetic basis for this separation is still enigmatic. We now report that B cell sequestration requires lineage-specific regulation of migratory receptors by the transcription factor Klf2. Moreover, using gene-targeted mice we show that altered splenic B cell migration confers a significant in vivo gain-of-function phenotype to FO B cells, including the ability to quickly respond to MZ-associated antigens and pathogens in a T cell-dependent manner. This work demonstrates that in wild-type animals, naive FO B cells are actively removed from the MZ, thus restricting their capacity to respond to blood-borne pathogens.
authors.affiliation: Department of Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232-2363, USA.
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Hoek
authors.forename: Laura E
authors.initials: LE
authors.lastname: Gordy
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Collins
authors.forename: Vrajesh V
authors.initials: VV
authors.lastname: Parekh
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Aune
authors.forename: Sebastian
authors.initials: S
authors.lastname: Joyce
authors.forename: James W
authors.initials: JW
authors.lastname: Thomas
authors.forename: Luc
authors.initials: L
authors.lastname: Van Kaer
authors.forename: Eric
authors.initials: E
authors.lastname: Sebzda
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology; D000955:Antigens, T-Independent / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D056724:Immunity, Humoral; D051741:Kruppel-Like Transcription Factors / Q000172:deficiency / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D054388:Receptors, CCR / Q000276:immunology; D013154:Spleen / Q000166:cytology* / Q000276:immunology*
chemical_list: D018941:Antigens, CD19; D000955:Antigens, T-Independent; C498314:Klf2 protein, mouse; D051741:Kruppel-Like Transcription Factors; D054388:Receptors, CCR