The following posting has received no response perhaps because it is too
cryptic:
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 gettysburg.edu
(717) 337-9171
(717) 337-6666 (fax)
