T follicular helper cells have distinct modes of migration and molecular signatures in naive and memory immune responses

Immunity. 2015 Apr 21;42(4):704-18. doi: 10.1016/j.immuni.2015.03.002. Epub 2015 Mar 31.


B helper follicular T (Tfh) cells are critical for long-term humoral immunity. However, it remains unclear how these cells are recruited and contribute to secondary immune responses. Here we show that primary Tfh cells segregate into follicular mantle (FM) and germinal center (GC) subpopulations that display distinct gene expression signatures. Restriction of the primary Tfh cell subpopulation in the GC was mediated by downregulation of chemotactic receptor EBI2. Following collapse of the GC, memory T cells persisted in the outer follicle where they scanned CD169(+) subcapsular sinus macrophages. Reactivation and intrafollicular expansion of these follicular memory T cells in the subcapsular region was followed by their extrafollicular dissemination via the lymphatic flow. These data suggest that Tfh cells integrate their antigen-experience history to focus T cell help within the GC during primary responses but act rapidly to provide systemic T cell help after re-exposure to the antigen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology
  • Cell Differentiation
  • Cell Lineage / genetics
  • Cell Lineage / immunology*
  • Cell Movement / immunology
  • Cell Proliferation
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Germinal Center / cytology*
  • Germinal Center / immunology
  • Immunity, Humoral*
  • Immunologic Memory
  • Mice
  • Mice, Knockout
  • Primary Cell Culture
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / immunology
  • Sialic Acid Binding Ig-like Lectin 1 / genetics
  • Sialic Acid Binding Ig-like Lectin 1 / immunology
  • Signal Transduction
  • T-Lymphocytes, Helper-Inducer / cytology*
  • T-Lymphocytes, Helper-Inducer / immunology


  • Gpr183 protein, mouse
  • Receptors, G-Protein-Coupled
  • Sialic Acid Binding Ig-like Lectin 1
  • Siglec1 protein, mouse