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Section: New Results

Immunology

Immune response, infection, antibodies, complementarity determining region (CDR)

Teleost Fish Mount Complex Clonal IgM and IgT Responses in Spleen Upon Systemic Viral Infection

Participant : Frédéric Cazals.

In collaboration with

  • R. Castro, L. Journeau, A. Benmansour and P. Boudinot (INRA Jouy-en-Josas, France)

  • H.P. Pham and A. Six (Univ. of Paris VI, France)

  • O. Bouchez (INRA Castanet Tolosan, France)

  • V. Giudicelli and M-P. Lefranc (IMGT / CNRS, Montpellier, France)

  • E. Quillet (INRA Jouy-en-Josas, France)

  • S. Fillatreau (Leibniz Institute, Berlin, Germany)

  • O. Sunyer (Univ. of Pennsylvania, USA)

Upon infection, B-lymphocytes expressing antibodies specific for the intruding pathogen develop clonal responses triggered by pathogen recognition via the B-cell receptor. The constant region of antibodies produced by such developing clones dictates their functional properties. In teleost fish, the clonal structure of B-cell responses and the respective contribution of the three isotypes IgM, IgD, and IdT remains unknown. The expression of IgM and IgT are mutually exclusive, leading to the existence of two B-cell subsets expressing either both IgM and IgD or only IgT. In [12] , we undertook a comprehensive analysis of the variable heavy chain (VH) domain repertoires of the IgM, IgD and IgT in spleen of homozygous isogenic rainbow trout (Onchorhynus mykiss), before and after challenge with a rhabdovirus, the Viral Hemorrhagic Septicemia Virus (VHSV), using CDR3-length spectratyping and pyrosequencing of immunoglobulin (Ig) transcripts. In healthy fish, we observed distinct repertories for IgM, IgD and IgT respectively, with a few amplified μ and τ junctions, suggesting the presence of IgM and IgT secreting cells in the spleen. In infected animals, we detected complex and highly diverse IgM responses involving all VH subgroups, and dominated by a few large public and private clones. A lower number of robust clonal responses involving only a few VH were detected for the mucosal IgT, indicating that both IgM + and IgT + spleen B cells responded to systemic infection but at different degrees. In contrast, the IgD response to the infection was faint. Although the IgD and IgT present different structural features and evolutionary origin compared to mammalian IgD and IgA respectively, their implication in the B-cell response evokes these mouse and human counterparts. Thus, it appears that the general properties of antibody responses were already in place in common ancestors of fish and mammals, and were globally conserved during evolution with possible functional convergences.