Memory is a hallmark of adaptive immunity, wherein lymphocytes mount a superior response to a previously encountered antigen. It has been speculated that epigenetic alterations in memory lymphocytes contribute to their functional distinction from their naive counterparts. However, the nature and extent of epigenetic alterations in memory compartments remain poorly characterized. Here we profile the DNA methylome and the transcriptome of B-lymphocyte subsets representing stages of the humoral immune response before and after antigen exposure in vivo from multiple humans. A significant percentage of activation-induced losses of DNA methylation mapped to transcription factor binding sites. An additional class of demethylated loci mapped to Alu elements across the genome and accompanied repression of DNA methyltransferase 3A. The activation-dependent DNA methylation changes were largely retained in the progeny of activated B cells, generating a similar epigenetic signature in downstream memory B cells and plasma cells with distinct transcriptional programs. These findings provide insights into the methylation dynamics of the genome during cellular differentiation in an immune response.

Aberrant DNA methylation commonly occurs in cancer cells where it has been implicated in the epigenetic silencing of tumor suppressor genes. Additional roles for DNA methylation, such as transcriptional activation, have been predicted but have yet to be clearly demonstrated. The BCL6 oncogene is implicated in the pathogenesis of germinal center–derived B cell lymphomas. We demonstrate that the intragenic CpG islands within the first intron of the human BCL6 locus were hypermethylated in lymphoma cells that expressed high amounts of BCL6 messenger RNA (mRNA). Inhibition of DNA methyltransferases decreased BCL6 mRNA abundance, suggesting a role for these methylated CpGs in positively regulating BCL6 transcription. The enhancer-blocking transcription factor CTCF bound to this intronic region in a methylation-sensitive manner. Depletion of CTCF by short hairpin RNA in neoplastic plasma cells that do not express BCL6 resulted in up-regulation of BCL6 transcription. These data indicate that BCL6 expression is maintained during lymphomagenesis in part through DNA methylation that prevents CTCF-mediated silencing.

Pharyngeal hairy polyps are rare lesions that present as a pedunculated mass that may arise from the oropharyngeal or nasopharyngeal regions of the pharynx. The mass has the potential to partially or completely obstruct pathways towards the trachea and/or esophagus resulting in respiratory distress and/or feeding difficulties respectively. They have a predilection for female infants of 6:1 with the vast majority of the cases occurring in the infantile period. We report 5 cases of the hairy polyp in female infants, one of which showed unusual presentation since it was diagnosed at ten months of age.

Tuberous sclerosis (TSC) is an autosomal-dominant genetic disease characterized by a spectrum of pathologic manifestations involving skin, brain, kidney, and heart. These manifestations include neuroectodermal, mesodermal, and skin lesions as well as a variety of associated tumors and hamartomas. We report an 11-year-old male with previously diagnosed TSC who presented with a laryngeal mass shown on histology to be fetal cellular rhabdomyoma. Cardiac rhabdomyomas are common in TSC patients, but to our knowledge, the association between TSC and extracardiac rhabdomyomas has not been previously reported.

No abstract