DCs in the GALT, unlike DCs found in other lymphoid tissues, synthesize retinoic acid, which has been shown to induce the expression of a distinct set of trafficking molecules on the surface of T cells that infiltrate the gut. So, the authors examined the effect of GALT-derived DCs on expression of the gut-specific trafficking molecules α4β7-integrin and CC-chemokine receptor 9 (CCR9) on B cells. Co-culture of B cells with DCs derived from Peyer's patches resulted in α4β7-integrinhiCCR9hi B cells. By contrast, co-culture of B cells with DCs isolated from peripheral lymph nodes induced α4β7-integrinlowCCR9low B cells. Interestingly, expression of these homing molecules by B cells could be induced, in the absence of DCs, by exogenous retinoic acid. Therefore, only DCs from the GALT, through the secretion of retinoic acid, induce gut-tropic B cells.
The authors then examined the ability of these B cells to produce IgA. Only Peyer's patch-derived DCs induced de novo class switching and secretion of IgA by B cells. Blocking of the retinoic acid receptor with the receptor antagonist LE540 decreased IgA secretion in these co-cultures. However, retinoic acid alone was not sufficient to induce IgA secretion, indicating that, although retinoic acid is involved, additional factors are required. Blocking of IL-6 or IL-5 (cytokines that are known to induce IgA responses) with specific antibodies, together with LE540 (but not on their own), lead to a reduction in IgA secretion.
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