The molecular mechanisms which underlie allorecognition in Botryllus and the origins of the vertebrate adaptive immune system

When two colonies of B. schlosseri come into close contact, they initiate a natural allorecognition reaction when terminal projections of the vasculature reach out from each individual and contact each other. Two outcomes can result from this interaction: either the vasculatures will fuse together and form a single chimeric colony with a common blood supply, or the two colonies will reject each other in a blood-based inflammatory reaction during which the interacting vasculature is destroyed and the two colonies no longer interact. This allorecognition reaction is controlled by a single, highly polymorphic locus called the FuHC (for fusion/histocompatibility). Two colonies will fuse together if they share one or both FuHC alleles, and will reject each other if there are no alleles in common. Genetically, this is analogous to allorecognition in the vertebrates, which is controlled by the Major Histocompatibility Complex (MHC), another single, highly polymorphic locus. Functionally, this resembles the missing-self recognition of vertebrate natural killer (NK) cells, where rejection by effector cells would be inhibited by the presence of a self MHC allele. Taking a forward genetic approach, we have recently identified a candidate FuHC gene by positional cloning. This gene encodes a highly polymorphic, type I transmembrane protein containing two tandem immunoglobulin domains, and by all characteristics is the allorecognition ligand. Thus the candidate FuHC provides the first structural link between allorecognition and the immunoglobulin based vertebrate adaptive immune system. In addition, this locus also appears to contain Fu/HC receptors, as a group of genes, called the fester family, have been identified which have characteristics suggesting their involvement in allorecognition. The FuHC locus is highly dynamic and we are continuing to study this locus.

Interaction

When the edges of two colonies meet, peripheral blood vessels, called ampullae, reach out and touch. This interaction will leand to one of two outcomes and is controlled by a single, highly polymorphic locus called the FuHC, for (fusion/histocompatibility)

Fusion

If the two colonies share at least one of the two FuHC alleles, the two ampullae will fuse together (arrows) to form a single colony which shares a common circulation.

Rejection

Colonies which do not share FuHC alleles will reject each other in a blood-based inflammation reaction which results in cell death and deposition near the ampullae, called points of rejection (arrows).