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Adaptive immunity of the type found in mammals is phylogenetically restricted to the jawed vertebrates; however, a second form of somatically diversifying receptors is present in the living jawless vertebrates, the lampreys and hagfishes. Unlike the immunoglobulin domain-based antibodies and T cell receptors of jawed vertebrates, the variable lymphocyte receptors (VLRs) of jawless vertebrates are based on leucine-rich repeat (LRR) proteins. One type of these, variable lymphocyte receptor B (VLRB), is expressed as both a cell surface receptor on B-like cells and as a soluble polymeric antibody, analogous to the immunoglobulins of jawed vertebrates. The genomic locus encoding VLRB consists of an incomplete germline gene with two regions that make up the invariant ends of the mature receptor separated by a noncoding intervening region. The germline VLRB gene is surrounded by hundreds of donor cassettes encoding LRR fragments that contribute to the variable portion of the mature receptor by incorporation into the locus in a process of stepwise somatic assembly. VLRB is expressed from a single allele as clonal receptors on B cell-like lymphocytes and secreted as antibody from plasma-like cells. Here we discuss the structure of the VLRB monomer and antibody, the genomic organisation of the complex VLRB locus in lamprey, the B-like lymphocytes that express VLRB, the role of cytidine deaminases in the assembly of mature VLRB and the applications of these lamprey antibodies in biomedicine.