A lamprey monoclonal VLR antibody recognizes a novel plasma cell antigen (P3020)

Abstract

Abstract Variable lymphocyte receptor B (VLRB) antibodies of the jawless sea lamprey are composed of leucine-rich repeat (LRR) units instead of the Ig-based units of conventional mammalian antibodies. Structural analyses of three monoclonal VLRB antibodies paired with their cognate antigens indicate that antigens bind to variable residues in the beta-sheets located on the inner concave surface of the solenoid VLRB protein and to a flexible loop structure protruding from the C-terminal LRR. We recently demonstrated that VLRB antibodies can be used in standard laboratory techniques such as flow immunocytometry, western blotting, immunoprecipitation and mass spectrometry-based protein identification. In an effort to identify novel biomarkers on human plasma cells, we screened a VLRB library generated from lamprey larvae immunized with human bone marrow of multiple myeloma patient and isolated a monoclonal VLRB antibody (MM3) that selectively recognized plasma cells from myeloma patients, normal individuals and two non-human primates, Rhesus macaque and Sooty mangabey monkeys. Surprisingly, screening of a diverse panel of human cell lines indicated expression of the MM3 antigen by two of nine B cell lines, but not by plasmacytoma cell lines. Trypsin and periodate sensitivity of the MM3 epitope suggested the glycoprotein nature of the cell membrane antigen. We conclude that the recombinant VLR MM3 antibody recognizes a novel plasma cell marker.