title: Dual nature of the adaptive immune system in lampreys.
abstract: Jawless vertebrates use variable lymphocyte receptors (VLR) comprised of leucine-rich-repeat (LRR) segments as counterparts of the immunoglobulin-based receptors that jawed vertebrates use for antigen recognition. Highly diverse VLR genes are somatically assembled by the insertion of variable LRR sequences into incomplete germline VLRA and VLRB genes. Here we show that in sea lampreys (Petromyzon marinus) VLRA and VLRB anticipatory receptors are expressed by separate lymphocyte populations by monoallelic VLRA or VLRB assembly, together with expression of cytosine deaminase 1 (CDA1) or 2 (CDA2), respectively. Distinctive gene expression profiles for VLRA(+) and VLRB(+) lymphocytes resemble those of mammalian T and B cells. Although both the VLRA and the VLRB cells proliferate in response to antigenic stimulation, only the VLRB lymphocytes bind native antigens and differentiate into VLR antibody-secreting cells. Conversely, VLRA lymphocytes respond preferentially to a classical T-cell mitogen and upregulate the expression of the pro-inflammatory cytokine genes interleukin-17 (IL-17) and macrophage migration inhibitory factor (MIF). The finding of T-like and B-like lymphocytes in lampreys offers new insight into the evolution of adaptive immunity.
authors.affiliation: Emory Vaccine Center and Department of Pathology and Laboratory Medicine, Emory University, 1462 Clifton Road North-East, Atlanta, Georgia 30322, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Guo
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hirano
authors.forename: Brantley R
authors.initials: BR
authors.lastname: Herrin
authors.forename: Jianxu
authors.initials: J
authors.lastname: Li
authors.forename: Cuiling
authors.initials: C
authors.lastname: Yu
authors.forename: Andrea
authors.initials: A
authors.lastname: Sadlonova
authors.forename: Max D
authors.initials: MD
authors.lastname: Cooper
mesh_terms: D000483:Alleles; D020816:Amino Acid Motifs; D000818:Animals; D000941:Antigens / Q000276:immunology; D005075:Biological Evolution; D043525:Cytosine Deaminase / Q000378:metabolism; D029941:Fish Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D020869:Gene Expression Profiling; D020381:Interleukin-17 / Q000378:metabolism; D007798:Lampreys / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism; D008934:Mitogens / Q000276:immunology; D010835:Phytohemagglutinins / Q000276:immunology; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
chemical_list: D000941:Antigens; D029941:Fish Proteins; D020381:Interleukin-17; D008263:Macrophage Migration-Inhibitory Factors; D008934:Mitogens; D010835:Phytohemagglutinins; D011971:Receptors, Immunologic; D043525:Cytosine Deaminase