Follicular B cell trafficking within the spleen actively restricts humoral immune responses.
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.
Hoek
Kristen L
KL
Department of Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232-2363, USA.
Gordy
Laura E
LE
Collins
Patrick L
PL
Parekh
Vrajesh V
VV
Aune
Thomas M
TM
Joyce
Sebastian
S
Thomas
James W
JW
Van Kaer
Luc
L
Sebzda
Eric
E
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*
D018941:Antigens, CD19; D000955:Antigens, T-Independent; C498314:Klf2 protein, mouse; D051741:Kruppel-Like Transcription Factors; D054388:Receptors, CCR