The Essential Role of anxA2 in Langerhans Cell Birbeck Granules Formation

Cells. 2020 Apr 15;9(4):974. doi: 10.3390/cells9040974.


Langerhans cells (LC) are the resident antigen presenting cells of the mucosal epithelium and play an essential role in initiating immune responses. LC are the only cells in the body to contain Birbeck granules (BG), which are unique cytoplasmic organelles comprised of c-type lectin langerin. Studies of BG have historically focused on morphological characterizations, but BG have also been implicated in viral antigen processing which suggests that they can serve a function in antiviral immunity. This study focused on investigating proteins that could be involved in BG formation to further characterize their structure using transmission electron microscopy (TEM). Here, we report a critical role for the protein annexin A2 (anxA2) in the proper formation of BG structures. When anxA2 expression is downregulated, langerin expression decreases, cytoplasmic BG are nearly ablated, and the presence of malformed BG-like structures increases. Furthermore, in the absence of anxA2, we found langerin was no longer localized to BG or BG-like structures. Taken together, these results indicate an essential role for anxA2 in facilitating the proper formation of BG.

Keywords: A2t; Birbeck granules; Langerhans cell; anxA2.

Publication types

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

MeSH terms

  • Annexin A2 / metabolism*
  • Antigens, CD
  • Cell Line
  • Cytoplasmic Granules / metabolism*
  • Cytoplasmic Granules / ultrastructure
  • Humans
  • Langerhans Cells / metabolism*
  • Langerhans Cells / ultrastructure
  • Lectins, C-Type
  • Mannose-Binding Lectins
  • Protein Subunits / metabolism
  • Protein Transport


  • Annexin A2
  • Antigens, CD
  • CD207 protein, human
  • Lectins, C-Type
  • Mannose-Binding Lectins
  • Protein Subunits