Portal de Periódicos da CAPES

One Cytokine, Two Isotypes

2000; American Thoracic Society; Volume: 162; Issue: supplement_2 Linguagem: Inglês

10.1164/ajrccm.162.supplement_2.ras-6

1535-4970

Donata Vercelli,

Immunotherapy and Immune Responses

You can’t do it all. This is probably the reason why for a long time researchers interested in IgE regulation paid little attention to other immunoglobulin (Ig) isotypes and to the conditions required for their production. The discovery that isotype switching is directed by cytokines (reviewed in References 1 and 2), and that interleukin 4 (IL-4) is specifically responsible for the induction of switching to IgE (3), spurred a vast effort to try and understand the cellular and molecular mechanisms underlying the effects of this cytokine. In article after article (ours included) the leitmotif in the studies of IL-4-dependent IgE regulation was the specificity of the effects of this cytokine, that is, how IL-4 secures the production of IgE, and only IgE. One cytokine, one isotype. Molecular studies of the IgE system made a major contribution to the identification of germline transcription as a key step in determining the isotype specificity of switching. The expression of germline transcripts reflects the cytokine-dependent activation of transcription from an I H region located upstream of the switch region subsequently targeted by recombination (4, 5). The germline proceed from the I H region through the switch region itself and then all the way through the Ig constant heavy chain (C H ) gene expressed as a result of switching. The germline transcripts produced after splicing contain the I H region directly joined to the C H transcript (reviewed in Reference 1). It is by now generally accepted that processed germline transcripts and/or the mechanism of germline transcription are required to increase the accessibility of chromatin at a specific switch region (the one through which transcription is activated by the cytokine), which thus becomes the preferred target for the recombination machinery (6). Even though this model awaits direct confirmation (7), it is strongly supported by an overwhelming amount of data from different experimental systems, first and foremost mice in which genes essential for germline transcription have been deleted by homologous recombination (8–14).