T cell help induces Myc transcriptional bursts in germinal center B cells during positive selection.

Antibody affinity maturation occurs in secondary lymphoid organs within germinal centers (GCs). At these sites, B cells mutate their antibody-encoding genes in the dark zone, followed by preferential selection of the high-affinity variants in the light zone by T cells. The strength of the T cell-derived selection signals is proportional to the B cell receptor affinity and to the magnitude of subsequent Myc expression. However, because the lifetime of Myc mRNA and its corresponding protein is very short, it remains unclear how T cells induce sustained Myc levels in positively selected B cells. Here, by direct visualization of mRNA and active transcription sites in situ, we found that an increase in transcriptional bursts promotes Myc expression during B cell positive selection in GCs. Elevated T cell help signals predominantly enhance the percentage of cells expressing Myc in GCs as opposed to augmenting the quantity of Myc transcripts per individual cell. Visualization of transcription start sites in situ revealed that T cell help promotes an increase in the frequency of transcriptional bursts at the Myc locus in GC B cells located primarily in the LZ apical rim. Thus, the rise in Myc, which governs positive selection of B cells in GCs, reflects an integration of transcriptional activity over time rather than an accumulation of transcripts at a specific time point.

Intervening in the acute phase of postradiation carotid blowout syndrome

Introduction: Acute carotid blowout syndrome (aCBS) is a severe complication of head and neck cancer (HNC). It can be defined as a rupture of the extracranial carotid arteries, or one of their branches, that causes life-threatening hemorrhage, and which nowadays can be treated with urgent endovascular intervention. Objective: We retrospectively evaluate the endovascular management of aCBS and its outcome in years of survival. Methods: Retrospectively, we describe our experience with endovascular control of aCBS in patients treated for HNC. We review the characteristics, pathology, endovascular treatment and morbidity and assess the gain in life years. Results: Nine individuals were included in this study. Four patients had been previously diagnosed with laryngeal squamous cell carcinoma (SCC), one with paranasal SCC, one with nasopharyngeal carcinoma and three with oral or maxillary adenocarcinoma. All subjects underwent radiotherapy and surgical excision to different extents. Twelve endovascular procedures were performed for injuries to the internal carotid artery (n = 3; 25%), external carotid artery (n = 1; 7%) or one of their branches (n = 8; 67%). Deconstructive methods were used in nine procedures, and three procedures were mainly reconstructive with deployment of covered stents. Total control of bleeding was achieved in all individuals with no intraprocedural complications. Conclusion: Endovascular therapy is an effective alternative for the management of exsanguinating CBS. In our series, this palliative therapy increased the overall patient survival by an estimated 9 months (AU)