Impaired Peyer's patch development in BOB.1/OBF.1-deficient mice

摘要

The transcriptional co-activator BOB.1/ OBF.1 is known to regulate expression of genes involved in B- and T-cell physiology. So far, severe developmental and functional defects of lymphocytes in spleen (SP) and lymph nodes (LNs) of BOB.1/OBF.1-deficient mice have been reported [1]. Here, we describe a so far unrecognized characteristic of BOB.1/OBF.1-deficient animals, a strong defect at multiple steps of Peyer's patch (PP) development. Analysis of adult BOB.1/OBF.1-deficient mice revealed significantly reduced numbers of PPs along the intestine with a clear reduction in size (Fig. 1A) due to decreased cellularity (Fig. 1B). We observed significantly reduced numbers of B cells, especially those that exhibit a mature phenotype characterized by surface IgD expression (Fig. 1B; Supporting Information Fig. S1 A). Moreover, we detected significantly reduced total and CD4~+ T cells as well as diminished macrophages and dendritic cells (DCs) in PPs of BOB.1/OBF.1~-/- mice (Fig. 1B). Besides, BOB.1/OBF.1~-/- mice revealed a disturbed PP microarchitecture (Fig. 1C; Supporting Information Fig. S2). While PPs of wild-type (WT) mice featured a distinct organization in B- and T-lymphocyte zones and clearly separated areas of IgM+ and IgD+ B cells, this architecture is lost upon BOB.1/OBF.1 ablation. Additionally, in BOB.1/OBF.1~-/- mice, CD11c+ DCs, which are predominantly located within the subepithelial dome of WT PPs, are reduced and instead more frequently located within the PP follicular area (Supporting Information Figs. S1A and S2).