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

• DOI: 10.1016/j.immuni.2011.03.024
• Publication Date: 2011-06-19T12:56:30Z
• Authors: Steven M. Kerfoot; Gur Yaari; Jaymin R. Patel; Kody L. Johnson; David G. Gonzalez; Steven H. Kleinstein; Ann M. Haberman
• Keywords: B-Lymphocytes; Immunology; Cell Differentiation; T-Lymphocytes, Helper-Inducer; Germinal Center; Mice; 03 medical and health sciences; Infectious Diseases; Phenotype; 0302 clinical medicine; Cell Movement; Immunology and Allergy; Animals; Antigens

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.