Germinal center B cell and T follicular helper cell development initiates in the interfollicular zone

Immunity. 2011 Jun 24;34(6):947-60. 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(hi)ICOS(hi)GL7(hi) Tfh cell phenotype within the follicle, but not for their initial differentiation in the IF zone.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*


  • Antigens