Class Isotype Switching

Class (Isotype) Switching Occurs During Immune Responses... 

IL-4 TH2 cells, mast cells, NK cells B cells, T cells, mast cells, macrophages Proliferation, isotype switching, induction of MHC class II expression... 

B.B., Crit. Rev. Immunol. 24, 297-320, 2004 Fiset, P.O., Cameron, L., and Hamid, Q., Local isotype switching to IgE in airway mucosa, J. Allergy Clin. Immunol. 116, 233-236, 2005 Min, I.M. and Seising, E., Antibody class switch recombination roles for switch seqences and mismatch repair proteins, Adv. Immunol. 87, 297-328, 2005 Apian, P.D., Causes of oncogenic chromosomal translocation. Trends Genet. 22, 46-55, 2006. 

Antibodies of the IgG, IgA and IgE classes are made later than IgM during a primary immune response, but account for most of the antibody that is made during a memory response. Although isotype switching and affinity maturation are independent processes, they usually occur simultaneously (Fish et al., 1989), so that the increased affinity of bivalent antibodies of isotypes other than IgM is rapidly enhanced. IgG antibody is the predominant isotype in plasma and lymph, while IgA antibody predominates at mucosal surfaces and in secretions from these surfaces. 

Antibodies to DNA consist of both IgM and IgG classes. Healthy individuals usually have low-affinity IgM antibodies to DNA however, if these undergo an isotype switch to IgG, they may become pathogenic. Tests for DNA antibodies help establish a diagnosis of SLE,... 

Growth of multi-potential stem cells, myeloid, erythroid, mast cells Increases MHC Class II expression on macrophages, promotes mast cell proliferation, promotes hematopoietic precursors, isotype switching in IgGl and IgE, T cell proliferation, activation of B cells from resting state, increased MHC Class II expression, proliferation in presence of Ag, increased IL-2R receptor expression... 

Substantial evidence has supported the role of IL-4 and IL-13 in the induction of IgE synthesis (194). Interleukin-4 and IL-13 are the only cytokines known that can induce IgE synthesis in vitro using the recombinant proteins (186,195). The role of IL-4 was initially identified in vitro, T-cell-derived IL-4 was able to induce IgE production by lipopolysaccharide (LPS)-stimulated murine B cells (196), and anti-IL-4/IL-4 receptor (IL-4R) antibodies inhibited IgE responses in experimental animals (197,198). The role of IL-4 in human IgE isotype switch in B cells from IgM to IgE has been established using normal unfractionated peripheral blood mononuclear cells (PBMCs) (199) and single B cells stimulated with murine and human T-cell clones (192,200). Interleukin-4 is produced by activated Th2-type CD4+ cells and Tc2 type CD8+ cells (201), mast cells, and basophils (202). Functions attributable to IL-4 include upregulation of surface CD23, MHC class II and IL-4 receptor expression on monocytes and B cells, and increased expression of VCAM-1 on endothelial cells. 

Class switching Change in the isotype of antibody produced after a B cell has encountered an antigen. 

Once the specificity of the antibody has been established, it can be further characterized with respect to it isotype. This may be relevant to its application, but is also important if class switch variants are to be detected. 

Figure 32.9. Schematic representation of Type I hypersensitivity. Induction Resident respiratory tract dendritic cells (DC) take and process antigen, mature, migrate to the draining lymph nodes, and present antigen to T lymphocytes. Activated T-lymphocytes, in turn, activate B-cell differentiation into antibody-producing plasma cells. IL-4 promotes Ig isotype class switching from IgM to IgE and promotes mast cell development. IgE is associated with mast cells. Elicitation Allergen crosslinks the mast-cell-bound IgE, thereby causing the release of preformed mediators and cytokines. (See Table 32.7.) Inflammation and bronchoconstriction occur.

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