Lymphotoxin-Dependent B Cell-FRC Crosstalk Promotes De Novo Follicle Formation and Antibody Production following Intestinal Helminth Infection

Cell Rep. 2016 May 17;15(7):1527-1541. doi: 10.1016/j.celrep.2016.04.023. Epub 2016 May 5.


Secondary lymphoid tissues provide specialized niches for the initiation of adaptive immune responses and undergo a remarkable expansion in response to inflammatory stimuli. Although the formation of B cell follicles was previously thought to be restricted to the postnatal period, we observed that the draining mesenteric lymph nodes (mLN) of helminth-infected mice form an extensive number of new, centrally located, B cell follicles in response to IL-4Rα-dependent inflammation. IL-4Rα signaling promoted LTα1β2 (lymphotoxin) expression by B cells, which then interacted with CCL19 positive stromal cells to promote lymphoid enlargement and the formation of germinal center containing B cell follicles. Importantly, de novo follicle formation functioned to promote both total and parasite-specific antibody production. These data reveal a role for type 2 inflammation in promoting stromal cell remodeling and de novo follicle formation by promoting B cell-stromal cell crosstalk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation / immunology*
  • B-Lymphocytes / metabolism*
  • Cell Proliferation
  • Chemokine CCL19 / metabolism
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Helminthiasis / immunology*
  • Helminthiasis / parasitology*
  • Interleukin-4 Receptor alpha Subunit / metabolism
  • Intestinal Diseases, Parasitic / immunology*
  • Intestinal Diseases, Parasitic / parasitology*
  • Lymph Nodes / parasitology
  • Lymph Nodes / pathology
  • Lymphotoxin beta Receptor / metabolism
  • Lymphotoxin-alpha / metabolism*
  • Mice, Inbred C57BL
  • Nematospiroides dubius / physiology*
  • Signal Transduction
  • Stromal Cells / pathology
  • T-Lymphocytes / immunology


  • Chemokine CCL19
  • Interleukin-4 Receptor alpha Subunit
  • Lymphotoxin beta Receptor
  • Lymphotoxin-alpha

Supplementary concepts

  • Intestinal helminthiasis