Early steps of IgA B cell differentiation.

The overall picture of IgA B cell differentiation to emerge from these studies is that sIgM-bearing 'virgin' B cells entering the Peyer's patches are subject to a microenvironment (most probably organ-specific stromal cells) which brings about initial or primary IgA switch differentiation. For reasons mentioned, this probably does not involve TGF-beta, which instead appears to operate on a cell, such as the CH12.LX B cell, which has already undergone the initial steps of IgA isotype switching. The next stage of IgA B cell differentiation involves a cell which expressed both sIgM and sIgA simultaneously and appears to produce C mu and C alpha mRNA transcripts in the absence of a deletional rearrangement. Whether this involves a 'transplicing' mechanism or some other mechanism has yet to be determined. Finally, committed IgA B cells emerge from the dual-bearing cell population which express only sIgA. These cells can migrate out of Peyer's patches and respond to various terminal differentiation factors such as IL-5, IL-6 and IFN-gamma.