T Cells That Help B Cells in Chronically Inflamed Tissues

Front Immunol. 2018 Aug 23;9:1924. doi: 10.3389/fimmu.2018.01924. eCollection 2018.


Chronically inflamed tissues commonly accrue lymphocyte aggregates that facilitate local T cell-B cell interactions. These aggregates can range from small, loosely arranged lymphocyte clusters to large, organized ectopic lymphoid structures. In some cases, ectopic lymphoid structures develop germinal centers that house prototypical T follicular helper (Tfh) cells with high expression of Bcl6, CXCR5, PD-1, and ICOS. However, in many chronically inflamed tissues, the T cells that interact with B cells show substantial differences from Tfh cells in their surface phenotypes, migratory capacity, and transcriptional regulation. This review discusses observations from multiple diseases and models in which tissue-infiltrating T cells produce factors associated with B cell help, including IL-21 and the B cell chemoattractant CXCL13, yet vary dramatically in their resemblance to Tfh cells. Particular attention is given to the PD-1hi CXCR5- Bcl6low T peripheral helper (Tph) cell population in rheumatoid arthritis, which infiltrates inflamed synovium through expression of chemokine receptors such as CCR2 and augments synovial B cell responses via CXCL13 and IL-21. The factors that regulate CD4+ T cell production of CXCL13 and IL-21 in these settings are also discussed. Understanding the range of T cell populations that can provide help to B cells within chronically inflamed tissues is essential to recognize these cells in diverse inflammatory conditions and to optimize either broad or selective therapeutic targeting of B cell-helper T cells.

Keywords: B cells; CXCL13; IL-21; T follicular helper cells; T peripheral helper cells; ectopic lymphoid follicle; ectopic lymphoid structure; tertiary lymphoid tissue.

Publication types

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

MeSH terms

  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / pathology
  • Chronic Disease
  • Cytokines / immunology
  • Germinal Center / immunology*
  • Germinal Center / pathology
  • Humans
  • Inflammation / immunology
  • Inflammation / metabolism
  • Proto-Oncogene Proteins c-bcl-6 / immunology
  • Synovial Membrane / immunology
  • Synovial Membrane / pathology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / pathology


  • BCL6 protein, human
  • Cytokines
  • Proto-Oncogene Proteins c-bcl-6