Immunoglobulin Isotypes

  • All isotypes can exist as monomers. Mature, naive B cells prior to activation express IgM and IgD on their surfaces. They may differentiate in germinal centers of lymph nodes by isotype switching (gene rearrangement; induced by CD40L then T-cell cytokines such as IL-2 IL-4, IL-5, IL-6 and IFN-γ) into plasma cells that secrete IgA, IgE, or IgG.
  • IgG
    • Main antibody in 2° response to an antigen.
    • Most abundant isotype in serum.
    • Fixes complement, opsonizes bacteria, neutralizes bacterial toxins and viruses.
    • Only isotype that crosses the placenta (provides infants with passive immunity).
  •  IgA
    • Prevents attachment of bacteria and viruses to mucous membranes; does not fix complement.
    • Monomer (in circulation) or dimer (with J chain when secreted).
    • B cells in mesenteric lymph nodes and Peyer’s patches are activated, migrate to lamina propria under intestinal mucosa → become plasma cells → synthesize IgA dimers (linked by J-chain) → IgA dimers bind to polymeric immunoglobulin receptor (PIgR) on basolateral surface of intestinal epithelial cells. Crosses epithelial cells by transcytosis. Portion of pIgR remains attached to antibody (secretory component) producing the complete secretory IgA molecule.
    • Protects against gut infections (eg, Giardia).
    • Most produced antibody overall, but has lower serum concentrations.
    • Released into secretions (tears, saliva, mucus) and breast milk.
    • Picks up secretory component from epithelial cells, which protects the Fc portion from luminal proteases.
  • IgM
    • Produced in the 1° (immediate) response to an antigen.
    • Fixes complement.
    • Cannot cross the placenta.
    • Antigen receptor on the surface of B cells.
    • Monomer on B cell, pentamer with J chain when secreted.
    • Pentamer enables avid binding to antigen while humoral response evolves.
  • IgD
    • Unclear function. Found on surface of many B cells and in serum.
  • IgE
    • Binds mast cells and basophils; cross-links when exposed to allergen, mediating immediate (type I) hypersensitivity through release of inflammatory mediators such as histamine.
    • Contributes to immunity to parasites by activating eosinophils.
    • Lowest concentration in serum.

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