Evolution of adaptive immunity: Implications of a third lymphocyte lineage in lampreys

An alternative antigen receptor, named the variable lymphocyte receptor (VLR), was first identified in lampreys in 2004. Since then, the mechanism of VLR diversification via somatic gene assembly and the function of VLR‐expressing lymphocytes have been the subject of much research. VLRs comprise leucine‐rich repeat (LRR) motifs and are found only in the most phylogenetically distant vertebrates from mammals, lampreys, and hagfish. Previous reports showed that VLRA and VLRB are reciprocally expressed by lymphocytes that resemble T‐ and B cells; however, more recent reports show that another VLR, VLRC, is expressed on a third lymphocyte lineage, which may be equivalent to γδ T cells. The existence of three major lymphocyte lineages – one B‐cell‐like and two T‐cell‐like – and their development in lampreys, parallels the mammalian adaptive immune system. This suggests that these three cell lineages were present in the common vertebrate ancestor approximately 500 million years ago. Hirano et al. showed that the antigen receptor VLRC is expressed on a third lymphocyte lineage, which may be equivalent to the γδ T‐cell lineage. The existence of three major lymphocyte lineages and their development patterns suggest that these cell lineages were present in the common vertebrate ancestor approximately 500 million years ago.