title: M cell pockets of human Peyer's patches are specialized extensions of germinal centers.
abstract: M cells in follicle-associated epithelium of Peyer's patches (PP) mediate antigen entrance into the underlying lymphoid tissue. To investigate the functional potential of B cells in this unique microcompartment, the expression of co-stimulatory molecules necessary for B-T cell interaction was examined in histologically normal human PP by three-color immunohistochemistry. In the M cell areas, CD80 / CD86 expression was much more frequent on memory (sIgD(-)CD20(+)) B cells than on naive (sIgD(+)CD20(+)) B cells. M cell areas identified by such co-expression of CD20 and CD80 / CD86 were always spatially 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 cells with a high level of CD80 / CD86 were CD20(lo)CD10(-)Bcl-2(+), and adjacent memory T cells (CD3(+)CD45R0(+)) often expressed CD40L (CD154). Autologous peripheral blood B-T cell cocultures with purified protein derivative as antigen showed that the sIgD(-)CD80 / CD86(hi)CD20(lo) phenotype could indeed be generated during cognate B-T interactions, concurrent with CD40L up-regulation on memory T cells. Thus, this M cell-associated phenotype might result from B-T cell interactions in the course of antigen presentation by memory B cells, with subsequent CD40 engagement by CD40L-expressing cognate memory T cells. We propose that this M cell-associated event contributes to memory B cell survival and diversification of intestinal immunity, representing a specialized limb of GC function.
authors.affiliation: Laboratory for Immunohistochemistry and Immunopathology, Institute of Pathology, University of Oslo, The National Hospital, Rikshospitalet, Oslo, Norway. takeshi.yamanaka@labmed.uio.no
authors.forename: T
authors.initials: T
authors.lastname: Yamanaka
authors.forename: A
authors.initials: A
authors.lastname: Straumfors
authors.forename: H
authors.initials: H
authors.lastname: Morton
authors.forename: O
authors.initials: O
authors.lastname: Fausa
authors.forename: P
authors.initials: P
authors.lastname: Brandtzaeg
authors.forename: I
authors.initials: I
authors.lastname: Farstad
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D018951:Antigens, CD20 / Q000032:analysis; D001402:B-Lymphocytes / Q000502:physiology; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000032:analysis; D023201:CD40 Ligand / Q000502:physiology; D002450:Cell Communication; D018920:Coculture Techniques; D018858:Germinal Center / Q000502:physiology*; D006801:Humans; D007156:Immunologic Memory; D008562:Membrane Glycoproteins / Q000032:analysis; D010581:Peyer's Patches / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000502:physiology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis
chemical_list: D015703:Antigens, CD; D018951:Antigens, CD20; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D023201:CD40 Ligand