Science Bite (3 min Oral Presentation) Lorne Infection and Immunity 2019

A new role for MHC II and C3: MHCII-C3 complex forms immunological synapse between B lymphocytes and Dendritic Cells (#55)

Patrick Schriek 1 , Jose Villadangos 1 2 , Justine Mintern 1
  1. Bio21 Institute, Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Victoria, Australia
  2. Peter Doherty Institute, Microbiology and Immunology, University of Melbourne, Melbourne, Victoria, Australia

The role of Major histocompatibility complex class II (MHC II) molecules in the antigen presentation to CD4+ T cells has been characterised over decades of research. Complement component 3 (C3) is the central component of the complement system and its activation induces protective functions against pathogens as part of the innate immune system. Here we describe a new function for both molecules, namely the binding of activated C3 to MHC II on the surface of dendritic cells, mediating the interaction with B cells.           
MHC II expression in dendritic cells (DCs) is tightly controlled genetically and post-translationally. We found in several genetically modified mouse strains that surface expression of MHC II in DCs strictly correlates with the deposition of extracellular C3. Investigations revealed that activated C3 binds specifically to the N-linked glycan of the MHC II α-chain on the surface of CD8+ DCs. C3 linking to MHC II was also observed in normal cells from WT mice, albeit the C3 accumulation was limited through ubiquitin-mediated regulation of MHC II surface expression. Mice with enriched MHC II-C3 surface complex formation contain fewer DCs but enriched B cells with surface expression of DC-typical proteins. Both, DC numbers and B cell abnormalities, were restored in mutant mice if mice also lacked C3 expression. Analysis revealed that B cells receive dendritic cell membrane fractions via trogocytosis, reinforced through the presence of the MHC II-C3 complex on the surface of DCs. First experiments with human peripheral blood mononuclear cells (PBMC) revealed that C3 surface deposition depends on HLA surface expression, indicting the validity for our finding in human the system. 
Our results show a new role for MHC II and C3 in the fundamental cell-cell interaction between DCs and B lymphocytes mediating the extraction of membrane proteins, that are transcriptionally not expressed by B cells. Further characterisation will decipher functional benefits gained by the B lymphocytes that captured additional surface molecules via trogocytosis.