Regulation of the IgE isotype switch: new insights on cytokine signals and the functions of epsilon germline transcripts.
In allergic responses, B cells are driven to undergo an immunoglobulin isotype switch, shifting from IgM to IgE synthesis. This process involves the rearrangement of germline DNA in the immunoglobulin heavy-chain locus and is stimulated by cytokines (IL-4 and IL-13) and CD40 activation. It is now evident that cytokine-induced 'germline' epsilon-RNA transcripts associate with DNA in the genomic switch region (S epsilon) to form DNA-RNA hybrid structures, which target nucleases in for deletional switch recombination. Alterations in cytokine production and signaling affect the efficiency of this process and are associated with inherited predisposition to allergy.
Oettgen
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HC
Division of Immunology, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, 02115, Boston, MA 02115, USA. Oettgen@a1.tch.harvard.edu
D000818:Animals; D005786:Gene Expression Regulation; D005854:Germ Cells; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D007073:Immunoglobulin E / Q000235:genetics*; D007139:Immunoglobulin epsilon-Chains / Q000235:genetics*; D018793:Interleukin-13 / Q000378:metabolism*; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000378:metabolism; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4 / Q000378:metabolism; D011995:Recombination, Genetic; D015398:Signal Transduction
C508181:IL13RA1 protein, human; D007139:Immunoglobulin epsilon-Chains; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D015847:Interleukin-4; D007073:Immunoglobulin E