Educational Appendix

Antibody Isotype

Antibodies can come in different varieties known as isotypes or classes. In placental mammals there are five antibody isotypes known as IgA, IgD, IgE, IgG, and IgM. They are each named with an "Ig" prefix that stands for immunoglobulin, a name sometimes used interchangeably with antibody, and differ in their biological properties, functional locations and ability to deal with different antigens, as depicted in the table.[1] The different suffixes of the antibody isotypes denote the different types of heavy chains the antibody contains, with each heavy chain class named alphabetically: α, γ, δ, ε, and μ. This gives rise to IgA, IgG, IgD, IgE, and IgM, respectively.

Antibody isotypes of mammals

Name Types Description Antibody complexes
IgA 2 Found in mucosal areas, such as the gut, respiratory tract and urogenital tract, and prevents colonization by pathogens.[2] Also found in saliva, tears, and breast milk. antibody-isotypes-of-mammals-graphic
IgD 1 Functions mainly as an antigen receptor on B cells that have not been exposed to antigens.[3] It has been shown to activate basophils and mast cells to produce antimicrobial factors.[4]
IgE 1 Binds to allergens and triggers histamine release from mast cells and basophils, and is involved in allergy. Also protects against parasitic worms.[5]
IgG 4 In its four forms, provides the majority of antibody-based immunity against invading pathogens.[5] The only antibody capable of crossing the placenta to give passive immunity to the fetus.
IgM 1 Expressed on the surface of B cells (monomer) and in a secreted form (pentamer) with very high avidity. Eliminates pathogens in the early stages of B cell-mediated (humoral) immunity before there is sufficient IgG.[3][5]

B Cell

The antibody isotype of a B cell changes during cell development and activation. Immature B cells, which have never been exposed to an antigen, express only the IgM+ isotype in a cell surface bound form. The B lymphocyte, in this ready-to-respond form, is known as a "naive B lymphocyte." The naive B lymphocyte expresses both surface IgM+ and IgD+. The co-expression of both of these immunoglobulin isotypes renders the B cell ready to respond to antigen.[6] B cell activation follows engagement of the cell-bound antibody molecule with an antigen, causing the cell to divide and differentiate into an antibody-producing cell called a plasma cell. In this activated form, the B cell starts to produce antibody in a secreted form rather than a membrane-bound form. Some daughter cells of the activated B cells undergo isotype switching, a mechanism that causes the production of antibodies to change from IgM or IgD to the other antibody isotypes, IgE, IgA, or IgG, that have defined roles in the immune system.

References

  1. Woof J and Burton D (2004) Human antibody-Fc receptor interactions illuminated by crystal structures. Nat Rev Immunol 4(2): 89-99.
  2. Underdown B and Schiff J (1986) Immunoglobulin A: strategic defense initiative at the mucosal surface.Annu Rev Immunol 4(1): 389-417.
  3. Geisberger R et al. (2006) The riddle of the dual expression of IgM and IgD. Immunology 118(4): 889-898.
  4. Chen K et al. (2009) Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell-stimulating programs in basophils. Nature Immunology 10(8): 889-898.
  5. Pier GB et al. (2004) Immunology, Infection, and Immunity. ASM Press.
  6. Goding J (1978) Allotypes of IgM and IgD receptors in the mouse: a probe for lymphocyte differentiation. Contemp Top Immunobiol 8: 203-43.