New evidences of conserved pathways in complement system dynamics from the colonial ascidian Botryllus schlosseri.

In recent years, it has been widely demonstrated that complement, although often depicted as a ‘first line of defense’, is more than just a defender against microbial intruders and acts as a tightly integrated surveillance system. It is not only important against microorganisms, but also for the clearance of apoptotic cells and corpses. Botryllus schlosseri belongs, as vertebrates, to the phylum Chordata and, for this phylogenetic trait, it is unanimously considered a reliable model organism for the studies of the evolution of the immune system. Moreover it is also characterized by a peculiar life cycle with a cyclical, massive apoptosis. This two key features render B. schlosseri a good research tool for the study of the evolution of the complement system. Here we report the first results on the expression of BsC3 and BsFactorB, both components of the alternative pathway (AP) of complement activation, which form the AP C3 convertase. Since studies on mammalian models have shown that 80 % of the observed complement response is derived from AP convertase-mediated C3 amplification, even if initially induced by the classical pathway (CP), studies of complement activation in an organism that lack the adaptive immunity, as B. schlosseri, could lead to a better comprehension of the AP cascade and the behavior of C3 convertase not only in invertebrates, but also in vertebrates, mammals included. As in mammals, BsC3 is highly transcribed at basal level and over-expressed after incubation with non self (zymosan) while BsFactorB always shows limited expression. In the presence of compstatin, a 13-residue cyclic peptide able to inhibit the activation of C3 by C3 convertases, the percentage of phagocytosing hemocytes collapses. In the presence of both zymosan and compstatin, the transcription of BsC3 by hemocytes increases with respect to cells exposed only to zymosan: this suggests the presence of a conserved molecular machinery able to control and modulate B. schlosseri as well as the mammalian complement.