Thus IgM+ B cells present in the LP can be either gut-experienced cells emigrating from the PP and ILF or naive B cells recruited from the blood by LTPR/ NIK-sufficient gut stromal cells. Although is it extremely difficult to estimate the extent to which these two pathways participate in recruitment of IgM+ B cells to LP in a normal gut, it is likely that IgA generated in GALT-deficient mice must be derived from the IgM+ B cells that were recruited in a NIK-dependent manner, switched in situ to IgA+ B cells, and further differentiated to IgA plasma cells in the LP. Indeed, activated IgM+ B cells expressing large amounts of AID and a-germline transcripts, as well as IgA+ cells, can be detected in LP preparations of GALT-deficient mice, namely, in LP of aly/aly after double reconstitution with BM and NIK-sufficient gut stromal cells (Suzuki et al. 2005). Furthermore, stromal cells isolated from the gut LP appear to support preferential switching to IgA+ B cells and differentiation to IgA plasma cells of activated IgM+ B cells regardless of their provenience (PP, MLN, or spleen), even in the absence of T cells (Fagarasan et al. 2001). IgA switch-inducing activity of LP stromal cells is due to their capacity to produce and secrete large amounts of active TGF-p, because anti-TGF-p antibodies drastically decrease the efficiency of switching to IgA. Further differentiation of IgA+ B cells to plasma cells is supported by IL-6, IL-10, and probably other cytokines or chemokines produced by LP stromal cells (Fagarasan et al. 2001). Thus gut stromal cells are capable not only of supporting recruitment of IgM+ B cells but also of facilitating their local differentiation to IgA plasma cells.
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