Little is known of the anatomical compartmentalization of colitogenic or regulatory T-cell responses in the murine transfer colitis model. Therefore, we analyzed the putative function of large intestinal dendritic cell (DC) aggregates, to which donor CD4 ؉ T cells selectively home before colitis becomes manifest. The co-stimulatory molecules MHC-II, CD40, CD80, and CD86 were expressed in DC aggregates. IL-23 was primarily absent from DC aggregates at all stages of disease but was expressed at high levels in the severely inflamed lamina propria. Interferon-␥ was up-regulated in the lamina propria during early and advanced disease, whereas in DC aggregates it was detectable to a significant degree only in fully developed colitis. In contrast, Foxp3, a marker of regulatory T cells, was expressed in DC aggregates on T-cell transfer, coinciding with the appearance of CD103 ؉ CD25 ؊ T cells in these clusters. Foxp3 was enriched in the CD103 ؉ T-cell fraction isolated from the lamina propria of diseased mice. T-cell grafts depleted of CD103 ؉ T cells generated similar numbers of colonic CD103؉ T cells as unfractionated T cells. We conclude that DC aggregates are structures involved in the expansion and/or differentiation of CD103 ؉ CD25 ؊ CD4
Activation-induced cytidine deaminase (AID) initiates somatic hypermutation (SHM) and class switch recombination (CSR) in activated B lymphocytes and is potentially implicated in genomic instability of B-cell malignancies. For unknown reasons, B-cell neoplasms often lack SHM and CSR in spite of high AID expression. Here, we show that primary mediastinal B-cell lymphoma (PMBL), an immunoglobulin (Ig)-negative lymphoma that possesses hypermutated, class-switched Ig genes, expresses high levels of AID with an intact primary structure but does not do CSR in 14 of 16 cases analyzed.
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