Marginal zone B cells acquire dendritic cell functions by trogocytosis

Science. 2022 Feb 11;375(6581):eabf7470. doi: 10.1126/science.abf7470. Epub 2022 Feb 11.

Abstract

Marginal zone (MZ) B cells produce broad-spectrum antibodies that protect against infection early in life. In some instances, antibody production requires MZ B cells to display pathogen antigens bound to major histocompatibility complex class II (MHC II) molecules to T cells. We describe the trogocytic acquisition of these molecules from conventional dendritic cells (cDCs). Complement component 3 (C3) binds to murine and human MHC II on cDCs. MZ B cells recognize C3 with complement receptor 2 (CR2) and trogocytose the MHC II-C3 complexes, which become exposed on their cell surface. The ubiquitin ligase MARCH1 limits the number of MHC II-C3 complexes displayed on cDCs to prevent their elimination through excessive trogocytosis. Capture of C3 by MHC II thus enables the transfer of cDC-like properties to MZ B cells.

Publication types

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

MeSH terms

  • Adult
  • Animals
  • Antigen Presentation
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cell Membrane / metabolism
  • Complement Activation
  • Complement C3 / immunology
  • Complement C3 / metabolism*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Female
  • HLA-D Antigens / immunology
  • HLA-D Antigens / metabolism
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Lymphoid Tissue / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Middle Aged
  • Receptors, Complement 3d / immunology
  • Receptors, Complement 3d / metabolism
  • T-Lymphocytes / immunology
  • Trogocytosis*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination

Substances

  • C3 protein, human
  • Complement C3
  • HLA-D Antigens
  • Histocompatibility Antigens Class II
  • Receptors, Complement 3d
  • MARCH1 protein, mouse
  • MARCHF1 protein, human
  • Ubiquitin-Protein Ligases