Interactions between fibroblastic reticular cells and B cells promote mesenteric lymph node lymphangiogenesis

Lalit Kumar Dubey, Praneeth Karempudi, Sanjiv A. Luther, Burkhard Ludewig, Nicola L. Harris

Research output: Contribution to journalArticleResearchpeer-review

27 Citations (Scopus)

Abstract

Lymphatic growth (lymphangiogenesis) within lymph nodes functions to promote dendritic cell entry and effector lymphocyte egress in response to infection or inflammation. Here we demonstrate a crucial role for lymphotoxin-beta receptor (LTβR) signaling to fibroblastic reticular cells (FRCs) by lymphotoxin-expressing B cells in driving mesenteric lymph node lymphangiogenesis following helminth infection. LTβR ligation on fibroblastic reticular cells leads to the production of B-cell-activating factor (BAF?F), which synergized with interleukin-4 (IL-4) to promote the production of the lymphangiogenic factors, vascular endothelial growth factors (VEGF)-A and VEGF-C, by B cells. In addition, the BAFF-IL-4 synergy augments expression of lymphotoxin by antigen-activated B cells, promoting further B cell-fibroblastic reticular cell interactions. These results underlie the importance of lymphotoxin-dependent B cell-FRC cross talk in driving the expansion of lymphatic networks that function to promote and maintain immune responsiveness.

Original languageEnglish
Article number367
Number of pages13
JournalNature Communications
Volume8
Issue number1
DOIs
Publication statusPublished - 1 Dec 2017
Externally publishedYes

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