Response to: 'Meanderings into the regulation of effector class by the immune system: derivation of the trauma model' by Melvin Cohn.

Cohn M. Meanderings into the regulation of effector class by the immune system: derivation of the trauma model. Scand J Immunol 2012;76:77-88 delves into the discussion of how the immune system might regulate the decision between the immune response effector classes, and in particular identifies some key questions that need to be asked to understand how different classes of immune response occurring at the same time might be able to remain coherent and discrete. This is a needed discussion that advances the field, and the experiments proposed will go a long way to increasing our understanding of effector class regulation. However, in my opinion, the author makes some strong statements requiring substantiation regarding the impossibility of the involvement of germline-selected recognitive events as participating in self/non-self discrimination. Furthermore, the present discussion ignores a large body of contemporary literature describing the function and specificity of FoxP3+ regulatory T cells (T(reg) ) and formulates a theory that specifically excludes a role for T(reg) in maintaining self-tolerance without placing the contemporary evidence in the context of that theory. Thus in my opinion, these shortcomings should be addressed by the author.

The zebrafish IgH locus contains multiple transcriptional regulatory regions.

Many fish have, in addition to IgM and IgD, a third isotype called IgZ or IgT. The ζ-chain locus is embedded among the Ig heavy chain V-, D- and J-elements in a manner reminiscent of the TcR δ/α locus. Isotype selection thus occurs during VDJ recombination, a process that is facilitated by intralocus transcription. Using in silico analyses and enhancer reporter vectors we identified 3 new regions within the zebrafish IgH locus through which transcription can be activated in catfish B-cell lines. Two of these, termed Eζi (Jζ to Cζ1 intronic) and Eζ3' regions flank the ζ-chain constant domain exons. A third region, Eδ3', resides downstream of the δ-chain exons. All regions contain predicted binding sites for transcription factors that contribute to B-cell specific transcription in fish and mammals. Each region also has proximal matrix attachment regions, which may further contribute to transcriptional activation and chromatin remodeling. We discuss possible roles for these regions during VDJ recombination.