Regulation of humoral immunity by complement

Immunity. 2012 Aug 24;37(2):199-207. doi: 10.1016/j.immuni.2012.08.002.


The complement system of innate immunity is important in regulating humoral immunity largely through the complement receptor CR2, which forms a coreceptor on B cells during antigen-induced activation. However, CR2 also retains antigens on follicular dendritic cells (FDCs). Display of antigen on FDCs is critical for clonal selection and affinity maturation of activated B cells. This review will discuss the role of complement in adaptive immunity in general with a focus on the interplay between CR2-associated antigen on B cells with CR2 expressed on FDCs. This latter interaction provides an opportunity for memory B cells to sample antigen over prolonged periods. The cocrystal structure of CR2 with its ligand C3d provides insight into how the complement system regulates access of antigen by B cells with implications for therapeutic manipulations to modulate aberrant B cell responses in the case of autoimmunity.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Antigens / immunology
  • Antigens, CD19 / immunology
  • Autoimmunity / immunology
  • B-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • Complement Activation / immunology
  • Complement C3d / chemistry
  • Complement C3d / immunology*
  • Complement C3d / metabolism
  • Dendritic Cells, Follicular / immunology*
  • Dendritic Cells, Follicular / metabolism
  • Humans
  • Immunity, Humoral / immunology*
  • Immunity, Innate
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Knockout
  • Receptors, Complement 3d / chemistry
  • Receptors, Complement 3d / immunology*
  • Receptors, Complement 3d / metabolism
  • Tetraspanin 28 / immunology


  • Antigens
  • Antigens, CD19
  • Receptors, Complement 3d
  • Tetraspanin 28
  • Complement C3d