M cell pockets of human Peyer's patches are specialized extensions of germinal centers

M cells in follicle-associated epithelium of Peyer's patches (PP) mediate a ntigen entrance into the underlying lymphoid tissue. To investigate the fun ctional potential of B cells in this unique microcompartment, the expressio n of co-stimulatory molecules necessary for B-T cell interaction was examin ed in histologically normal human PP by three-color immunohistochemistry. I n the M cell areas, CD80/CD86 expression was much more frequent on memory ( slgD(-)CD20(+)) B cells than on naive (slgD(+)CD20(+)) B cells. M cell area s identified by such co-expression of CD20 and CD80/CD86 were always spatia lly related to germinal centers (GC). Contrary to the GC B cell phenotype ( sIgD(-)CD20(+)CD80/86(hi)CD10(+)Bcl-2(-)), however, M cell-associated B cel ls with a high level of CD80/CD86 were CD20(lo)CD10(-)Bcl-2(+), and adjacen t memory T cells (CD3(+)CD45R0(+)) often expressed CD40L (CD154). Autologou s peripheral blood B-T cell cocultures with purified protein derivative as antigen showed that the sIgD-CD80/CD86(hi)CD20(lo) phenotype could indeed b e generated during cognate B-T interactions, concurrent with CD40L up-regul ation on memory T cells. Thus, this M cell-associated phenotype might resul t from B-T cell interactions in the course of antigen presentation by memor y B cells, with subsequent CD40 engagement by CD40L-expressing cognate memo ry T cells. We propose that this M cell-associated event contributes to mem ory B cell survival and diversification of intestinal immunity, representin g a specialized limb of GC function.