Germinal Center B Cell and T Follicular Helper Cell Development Initiates in the Interfollicular Zone

• Published in: Immunity (Cambridge, Mass.) Vol. 34; no. 6; pp. 947 - 960
• Main Authors: Kerfoot, Steven M., Yaari, Gur, Patel, Jaymin R., Johnson, Kody L., Gonzalez, David G., Kleinstein, Steven H., Haberman, Ann M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.06.2011
• Subjects: Animals; Antigens - immunology; B-Lymphocytes - cytology; B-Lymphocytes - immunology; Cell Differentiation; Cell Movement; Germinal Center - cytology; Germinal Center - immunology; Mice; Phenotype; T-Lymphocytes, Helper-Inducer - cytology; T-Lymphocytes, Helper-Inducer - immunology
• ISSN: 1074-7613; 1097-4180; 1097-4180
• DOI: 10.1016/j.immuni.2011.03.024

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 hiICOS hiGL7 hi Tfh cell phenotype within the follicle, but not for their initial differentiation in the IF zone. ► After immunization, responding T and B cells home to and interact in the IF zone ► GC B cell and Tfh cell commitment in the IF zone precedes entry into the follicle ► The Tfh cell phenotype is induced globally, but maintained on only a subset of T cells ► Tfh cells differentiate, but are not maintained, in the absence of cognate B cells