Penetration of antibody-opsonized cells by the membrane attack complex of complement promotes Ca2+ influx and induces streamers

We have reported that during complement-mediated cytolysis of B cells promoted by the CD20 mAbs rituximab or ofatumumab (OFA), long, thin structures that we call streamers (>= 3 cell diameters) are rapidly generated and grow out from the cell surface. Streamers appear before cells are killed and contain opsonizing mAbs and membrane lipids. By exploiting the differential Ca2+ requirements of discrete steps in the complement cascade, we determined that mAb-opsonized cells first tagged with C3b using C5-depleted serum are killed on addition of serum and EDTA, but the cells do not produce streamers. Also, cells first opsonized with OFA are lysed in serum containing Mg-EGTA by the alternative complement pathway but streamers are not produced. These findings indicate that Ca2+ influx is necessary for streamer formation. Other mAbs that promote complement-mediated cytolysis also induce streamers on target cells. Streamer-like structures called nanotubes have been reported in several cellular systems, and are thought to promote intercellular communication/signaling. We tested whether this signaling could influence the susceptibility of neighboring cells contacted by streamers to complement attack and found that complement-mediated cytolysis of OFA-opsonized cells increases the resistance of unopsonized indicator cell populations to subsequent lysis when these cells are exposed to OFA and complement

Fate of trace metals in anaerobic digestion

© Springer International Publishing Switzerland 2015. A challenging, and largely uncharted, area of research in the field of anaerobic digestion science and technology is in understanding the roles of trace metals in enabling biogas production. This is a major knowledge gap and a multifaceted problem involving metal chemistry; physical interactions of metal and solids; microbiology; and technology optimization. Moreover, the fate of trace metals, and the chemical speciation and transport of trace metals in environments— often agricultural lands receiving discharge waters from anaerobic digestion processes— simultaneously represents challenges for environmental protection and opportunities to close process loops in anaerobic digestion.The authors acknowledge funding within the framework of the COST Action 1302 (‘European Network on Ecological Roles of Trace Metals in Anaerobic Biotechnologies’). GC is supported by a European Research Council Starting Grant (‘3C-BIOTECH; No. 261330).Peer Reviewe

Complement is activated by IgG hexamers assembled at the cell surface

Complement activation by antibodies bound to pathogens, tumors, and self antigens is a critical feature of natural immune defense, a number of disease processes, and immunotherapies. How antibodies activate the complement cascade, however, is poorly understood. We found that specific noncovalent interactions between Fc segments of immunoglobulin G (IgG) antibodies resulted in the formation of ordered antibody hexamers after antigen binding on cells. These hexamers recruited and activated C1, the first component of complement, thereby triggering the complement cascade. The interactions between neighboring Fc segments could be manipulated to block, reconstitute, and enhance complement activation and killing of target cells, using all four human IgG subclasses. We offer a general model for understanding antibody-mediated complement activation and the design of antibody therapeutics with enhanced efficacy