We were unable to find circulating pro-apoptotic factors in PAH patients that would support the EC apoptosis hypothesis of PAH. It is important to mention that we used HUVECs in our study and that, ideally, PS-341 in vivo patients’ own pulmonary ECs should be used to study pro-apoptotic activities of circulating IgG. Nevertheless, our study demonstrates that

circulating IgG from AECA-positive patients differ bioactively between diseases and cannot, therefore, be incorporated in a general cause–consequence relationship solely on the basis of their shared feature of binding to EC. Special thanks go to Drs B. Broers (cardiologist) from the Orbis Medisch Centrum in Sittard-Geleen, the Netherlands, for recruitment of PAH patients. The authors also thank N. Deckers from the Cardiovascular Research Institute Maastricht Selleck Silmitasertib (CARIM), the Netherlands, for his excellent technical assistance and advice with regard to the RT–CES™ assays. This research was supported by financially Actelion Pharmaceuticals Nederland BV (Woerden, the Netherlands). The authors declare that they have no conflict of interests. “
“Rapidly induced, specific Ab generated in extrafollicular foci are important components of early immune protection to influenza virus.

The signal(s) that prompt B cells to participate in extrafollicular rather than germinal center responses are incompletely understood. To study the regulation of early B-cell differentiation events following influenza infection, we exploited earlier findings of a strong contribution of C12 idiotype-expressing B cells to the primary HA-specific response against influenza A/PR/8/34. Using an idiotype-specific mAb to C12 and labeled HA, in conjunction with multicolor flow cytometry, we followed the fate of C12Id-expressing influenza HA-specific B cells in WT BALB/c mice, requiring neither genetic manipulation Carnitine palmitoyltransferase II nor adoptive cell transfer. Our studies demonstrate that HA-specific C12Id+ B cells are phenotypically indistinguishable from follicular B cells. While they induced both extrafollicular and germinal

center responses, extrafollicular responses were strongly predominant. Provision of increased HA-specific T-cell help increased the magnitude of the extrafollicular response, but did not shift the C12Id+ response toward germinal center formation. Collectively the data are consistent with the hypothesis that B-cell fate determination following activation is a stochastic process in which infection-induced innate signals might drive the preferential expansion of the early extrafollicular response. Influenza virus infection-induced anti-viral Ab can contribute to survival from primary and secondary infection 1–7. Rapid B-cell responses in the local respiratory tract draining mediastinal LN (MedLN) are induced as early as 48–72 h after infection 8.