Lymphatic endothelial cells regulate B-cell homing to lymph nodes via a NIK-dependent mechanism

Jie Yang, Siya Zhang, Lingyun Zhang, Xiaoping Xie, Hui Wang, Zuliang Jie, Meidi Gu, Jin Young Yang, Xuhong Cheng, Shao Cong Sun

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

B cells home to the lymph nodes (LNs) via high endothelial venules (HEVs) under the guidance of chemokines, particularly CXCL13. However, as CXCL13 is not directly made in HEVs, the molecular mechanism mediating B-cell homing to LNs has remained unclear. We show here that nuclear factor (NF)-κB-inducing kinase (NIK), a kinase mediating activation of the noncanonical NF-κB pathway, functions in lymphatic endothelial cells (LECs) to regulate B-cell homing to LNs. LEC-conditional deletion of NIK in mice did not affect the integrity or global function of lymphatic vessels but caused a severe reduction in the frequency of B cells in LNs. The LEC-specific NIK deficiency did not affect the survival of B cells or the frequency of B cells in the spleen. B-cell adoptive transfer studies revealed that the LEC-specific NIK deletion impairs the ability of LNs to recruit B cells. We further show that NIK mediates expression of the chemokines CXCL13 and CCL19 in LECs. Although CCL19 is also expressed in blood endothelial cells (BECs), CXCL13 is not produced in BECs. These results suggest that NIK regulates naive B-cell homing to LNs via mediating production of the B-cell homing chemokine CXCL13 in LECs.

Original languageEnglish (US)
Pages (from-to)165-177
Number of pages13
JournalCellular and Molecular Immunology
Volume16
Issue number2
DOIs
StatePublished - Feb 1 2019

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

MD Anderson CCSG core facilities

  • Flow Cytometry and Cellular Imaging Facility
  • Research Animal Support Facility

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