Adaptive immunity in jawless fish

Jawless vertebrates do not have immunoglobulins (Igs), the key proteins to B-cells and T-cells. However, they do possess a system of leucine-rich repeat (LRR) proteins that make up variable lymphocyte receptors (VLRs). This system can produce roughly the same number of potential receptors that the Ig-based system found in jawed vertebrates can.[4] Instead of recombination-activating genes (RAGs), genes coding for VLRs can be altered by a family of cytidine deaminases known as APOBEC, possibly through gene conversion.[5] Cytidine deaminase 1 is associated with the assembly of VLRA and VLRC and cytidine deaminase 2 appears to assemble VLRB.[1][3]

The gene expression profiles of lymphocyte-like cells (LLCs) in jawless vertebrates indicate that VLRB⁺ LLCs and B cells share a common ancestor, and VLRA⁺ and VLRC⁺ LLCs and T cells share a common ancestor.[6] Like B cells and T cells, the development of VLRB⁺ LLCs is spatially separated from the development of VLRA⁺ and VLRC⁺ LLCs. VLRB⁺ LLCs and B cells develop in hematopoietic tissues: VLRB⁺ LLCs develop in the typhlosole and kidneys and B cells develop in bone marrow. VLRA⁺ and VLRC⁺ LLCs develop in a thymus-like organ called the thymoid, similar to T cells developing in the thymus.[7] VLRB molecules and B cells can directly bind to antigens and VLRB-transfected cells secrete VLRB protein products, similar to B cells in jawed vertebrates. VLRA⁺ LLCs were unable to bind Bacillus anthracis, Escherichia coli, Salmonella typhimurium, or Streptococcus pneumoniae before or after immunization, suggesting that VLRAs require antigen processing like TCRs.[1] However, MHCs or MHC-like molecules that could present processed antigens have not been found in lampreys,[8] and some VLRAs expressed in yeast were able to directly bind to antigens.[9] The antigen binding of VLRCs has not been studied.[10] However, the VLRC gene is close in proximity and sequence to the VLRA gene and the two are often co-expressed in LLCs, suggesting that both are TCR-like receptors.[3]

• Flajnik, Martin F. (19 March 2018). "A cold-blooded view of adaptive immunity". Nature Reviews Immunology. 18 (7): 438–453. doi:10.1038/s41577-018-0003-9. PMC 6084782. PMID 29556016.