class switching

Ralph A. Sorensen Ralph.A.Sorensen at CC.GETTYSBURG.EDU
Fri Jul 23 07:58:57 EST 1993

The following posting has received no response perhaps because it is too 

   Recent reports on the CD40L gene responsible for x-linked hyper IgM 
syndrome   (HIM) pull together a lot of data about the cytokine control of 
class switching.   Two patterns emerge. IL-2, IL-10, and TGF-beta control 
IgG1-3 and IgA   secretion. IL-4 controls IgG4 and IgE secretion. My 
question concerns IgA.   Given the order of constant chain genes in the 
human, is the IgA in the former   case IgA1? Was IgA2 looked for in the 
latter case? Just wondering.

Let me expand. My fundamental question is whether or not there is a 
hierarchy to class switching. The fact that TH1 and TH2 cells produce 
mutually-exclusive patterns of cytokine secretion and that these respective 
cytokine spectra control isotypes that roughly fall into two serial groups 
in the constant chain gene suggests a hierarchy. Might TH2 cells initially 
switch the B cell V(D)J subgene to the gamma-4 subgene and subsequently 
control downstream IgG4 and IgE synthesis? Might TH1 cells initially switch 
to the gamma-3 subgene and subsequently control downstream IgG1, IgG2, and 
IgA1 synthesis? (But why stop at Ig4?) And what about TH2 control of IgA2? 
Am I all wet? The apparent match between the cytokines controlled and the 
order of the subgenes suggests this hypothesis. Is there supportive data?

                                                            Ralph A. Sorensen
                                                            Biology Department
                                                            Gettysburg College
                                                            rsorense at
                                                            (717) 337-9171
                                                            (717) 337-6666 (fax)

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