title: Germinal center B cell and T follicular helper cell development initiates in the interfollicular zone.
abstract: We identify the interfollicular (IF) zone as the site where germinal center B cell and T follicular helper (Tfh) cell differentiation initiates. For the first 2 days postimmunization, antigen-specific T and B cells remained confined within the IF zone, formed long-lived interactions, and upregulated the transcriptional repressor Bcl6. T cells also acquired the Tfh cell markers CXCR5, PD-1, and GL7. Responding B and T cells migrated to the follicle interior directly from the IF zone, T cell immigration preceding B cells by 1 day. Notably, in the absence of cognate B cells, Tfh cells still formed and migrated to the follicle. However, without such B cells, PD-1, ICOS, and GL7 were no longer expressed on follicular Bcl6(hi) T cells that nevertheless persisted in the follicle. Thus, Ag-specific B cells are required for the maintenance of the PD-1(hi)ICOS(hi)GL7(hi) Tfh cell phenotype within the follicle, but not for their initial differentiation in the IF zone.
authors.affiliation: Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT 06519, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Kerfoot
authors.forename: Gur
authors.initials: G
authors.lastname: Yaari
authors.forename: Jaymin R
authors.initials: JR
authors.lastname: Patel
authors.forename: Kody L
authors.initials: KL
authors.lastname: Johnson
authors.forename: David G
authors.initials: DG
authors.lastname: Gonzalez
authors.forename: Steven H
authors.initials: SH
authors.lastname: Kleinstein
authors.forename: Ann M
authors.initials: AM
authors.lastname: Haberman
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D002465:Cell Movement; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D051379:Mice; D010641:Phenotype; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*
chemical_list: D000941:Antigens