Nature Reviews Immunology | AoP, published online 12 June 2009; doi:10.1038/nri2590
E vO L u t I O N
A common solution to an age-old problem
A study of adaptive immunity in sea self-reactive T cells. Max Cooper homing to the thymus and T cell line- lampreys — a type of jawless verte- and colleagues now show that dual age commitment and function, such brate from which jawed vertebrates recognition and response arms of as CCR9, Notch1, CD45, CXCR2 (the diverged around 500 million years the adaptive immune system have receptor for interleukin-8 (IL-8)), IL17 ago — has shown the evolution of a evolved independently in jawless and MIF. In line with earlier studies common solution to the problem of vertebrates. showing that VLRB+ cells resemble preventing autoimmunity, according Using monoclonal antibodies spe- B cells in terms of the production of to Max Cooper and colleagues. cific for VLRA or VLRB, they identi- soluble VLRB ‘antibody’ in response The ability to recall previous fied discrete VLRA+ and VLRB+ to antigen, the VLRB+ cells in this encounters with a nearly unlimited lymphocyte-like cell populations in study had a gene expression profile variety of antigens, which is the the peripheral lymphoid tissues of that was similar to that of B cells. The hallmark of adaptive immunity, lamprey larvae. VLRA+ cells were expression of IL-8 and IL-17 receptor requires the generation of clonally shown to have assembled mature by VLRB+ cells indicates the potential diverse receptors. This is achieved VLRA gene configurations and to for reciprocal interactions between by V(D)J recombination of B cell express VLRA transcripts exclusively, VLRA+ and VLRB+ cells. receptor (BCR) and T cell receptor and the same relationship held for Following the immunization (TCR) genes in jawed vertebrates, VLRB gene assembly and expression of lamprey with Bacillus anthracis, whereas jawless vertebrates insert by VLRB+ cells. Mature and germline VLRA+ and VLRB+ cells proliferated variable leucine-rich repeat segments VLRA configurations were found in to a similar extent, but VLRA+ cells into incomplete germline variable equal proportions in VLRA+ cells, that bind B. anthracis spores could lymphocyte receptor VLRA and which shows that there is monoallelic not be found before or after immu- VLRB genes. But the development of VLRA gene assembly (similar to the nization. This suggests that VLRA+ a randomly generated receptor reper- TCR and BCR genes and as has been cells might recognize processed toire creates a risk of autoimmunity. previously shown for VLRB). rather than native antigens in a man- In jawed vertebrates, part of the VLRA+ and VLRB+ cell popula- ner analogous to T cells. In contrast solution to this problem has been tions had different gene expression to VLRB+ cells, VLRA+ cells did not the evolution of separate but inter- profiles. Notably, many of the genes secrete B. anthracis-specific antibod- acting lymphocyte populations that were selectively expressed by ies, which indicates that VLRA pro- — CD4+ T cells recognise antigen and VLRA+ cells are orthologous to genes teins, similarly to TCR proteins, are help B cells respond to antigen — with that are typically expressed by T cells expressed exclusively as transmem- a mechanism for selection against and are required for precursor cell brane molecules. In support of the analogy between VLRA+ cells in jaw- less vertebrates and T cells in jawed vertebrates, VLRA+ cells responded more vigorously than VLRB+ cells to a classical T cell mitogen. So, the discovery of independently evolved lymphocyte populations in lamprey that are analogous to B cells and T cells shows the importance of this division of labour in adaptive immunity. However, researchers have so far failed to find an equiva- lent of the thymus in lamprey and it is unclear whether VLRA+ cells undergo repertoire selection to avoid autoimmunity. Kirsty Minton
ORIGINAL RESEARCH PAPER Guo, P. et al.
Dual nature of the adaptive immune system in lampreys. Nature 27 May 2009 (doi:10.1038/ nature08068)