Diversity of complement factor B/C2 in the common carp (Cyprinus carpio): three isotypes of B/C2-A expressed in different tissues.

Complement factor B and C2 are two critical proteases for complement activation. Some bony fish have been reported to possess duplicated genes for B/C2, but there is no direct evidence regarding possible functional divergence. Here, we report the isolation of the second and third isotypes of carp B/C2-A, a close relative of other bony fish B reported to date, and designated B/C2-A2 and B/C2-A3. B/C2-A1 (previously reported B/C2-A) and B/C2-A2 share 78% amino acid identity and are synthesized mainly in hepatopancreas. On the other hand, B/C2-A3 showed less (approximately 60%) sequence identity with the other two isotypes. It was expressed mainly in kidney and spleen, and was up-regulated after injection of carp with scleroglucan or sodium alginate, known immunostimulants for fish. Phylogenetic analysis suggests that B/C2-A3 diverged before separation of carp and zebrafish. B/C2-A3 represent a novel B/C2-lineage functioning as an acute phase reactant in cyprinid fish.