Engineering a reporter cell line to mimic the high oligomannose presenting surface immunoglobulin of follicular lymphoma B cells. 2021

Butaek Lim, and LeNaiya Kydd, and Justyn Jaworski
Department of Bioengineering, University of Texas at Arlington, 500 UTA Blvd., Arlington, TX, 76019, USA.

Subtypes of B cell non-Hodgkin's lymphomas, including follicular lymphomas, have shown a unique high oligomannose presentation on their immunoglobulins that will interact with natural receptors of the innate immunity, reportedly causing stimulation and proliferation. From deep sequencing of the variable heavy and light chain sequences of follicular lymphoma involved tissue sections, we identified the consensus variable sequences possessing glycosylation sites at the complementarity determining region. Using this information, we developed a cell line, referred to here as BZ, which displays the consensus variable segments as part of a surface antibody (IgM) and confirmed its presentation of high oligomannose on the heavy chain both in vitro and in vivo. An mCherry expressing variant provided a reporter cell line displaying the high oligomannose surface biomarker while affording clear fluorescent signals for FACS screening as well as for fluorescent in vivo imaging of ectopic xenograft tumors. In developing this reporter cell line that displays the biomarker glycan of follicular lymphoma, we provide a tool that may be used for future screening and validation of receptive moieties for selectively binding high oligomannose for development of targeted diagnostics or therapeutics to such B cell malignancies that display this unique glycan.

UI MeSH Term Description Entries
D007075 Immunoglobulin M A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally was called a macroglobulin. Gamma Globulin, 19S,IgM,IgM Antibody,IgM1,IgM2,19S Gamma Globulin,Antibody, IgM
D008224 Lymphoma, Follicular Malignant lymphoma in which the lymphomatous cells are clustered into identifiable nodules within the LYMPH NODES. The nodules resemble to some extent the GERMINAL CENTER of lymph node follicles and most likely represent neoplastic proliferation of lymph node-derived follicular center B-LYMPHOCYTES. Brill-Symmers Disease,Follicular Lymphoma,Lymphoma, Giant Follicular,Lymphoma, Nodular,Follicular Large-Cell Lymphoma,Follicular Lymphoma, Giant,Follicular Lymphoma, Grade 1,Follicular Lymphoma, Grade 2,Follicular Lymphoma, Grade 3,Follicular Mixed-Cell Lymphoma,Giant Follicular Lymphoma,Histiocytic Lymphoma, Nodular,Large Lymphoid Lymphoma, Nodular,Large-Cell Lymphoma, Follicular,Lymphocytic Lymphoma, Nodular, Poorly Differentiated,Lymphocytic Lymphoma, Nodular, Poorly-Differentiated,Lymphoma, Follicular Large-Cell,Lymphoma, Follicular, Grade 1,Lymphoma, Follicular, Grade 2,Lymphoma, Follicular, Grade 3,Lymphoma, Follicular, Mixed Cell,Lymphoma, Follicular, Mixed Lymphocytic-Histiocytic,Lymphoma, Follicular, Mixed Small and Large Lymphoid,Lymphoma, Follicular, Small and Large Cleaved Cell,Lymphoma, Follicular, Small and Large Cleaved-Cell,Lymphoma, Histiocytic, Nodular,Lymphoma, Large Cell, Follicular,Lymphoma, Large Lymphoid, Nodular,Lymphoma, Large-Cell, Follicular,Lymphoma, Lymphocytic, Nodular, Poorly Differentiated,Lymphoma, Lymphocytic, Nodular, Poorly-Differentiated,Lymphoma, Mixed-Cell, Follicular,Lymphoma, Nodular, Large Follicular Center Cell,Lymphoma, Nodular, Large Follicular Center-Cell,Lymphoma, Nodular, Mixed Lymphocytic Histiocytic,Lymphoma, Nodular, Mixed Lymphocytic-Histiocytic,Lymphoma, Nodular, Mixed Small and Large Cell,Lymphoma, Small Cleaved Cell, Follicular,Lymphoma, Small Cleaved-Cell, Follicular,Lymphoma, Small Follicular Center-Cell,Lymphoma, Small Lymphoid, Follicular,Mixed-Cell Lymphoma, Follicular,Nodular Large Follicular Center-Cell Lymphoma,Small Cleaved-Cell Lymphoma, Follicular,Small Follicular Center-Cell Lymphoma,Brill Symmers Disease,Disease, Brill-Symmers,Follicular Large Cell Lymphoma,Follicular Large-Cell Lymphomas,Follicular Lymphomas,Follicular Lymphomas, Giant,Follicular Mixed Cell Lymphoma,Follicular Mixed-Cell Lymphomas,Giant Follicular Lymphomas,Histiocytic Lymphomas, Nodular,Large Cell Lymphoma, Follicular,Large-Cell Lymphomas, Follicular,Lymphoma, Follicular Large Cell,Lymphoma, Follicular Mixed-Cell,Lymphoma, Nodular Histiocytic,Lymphoma, Small Follicular Center Cell,Lymphomas, Follicular,Lymphomas, Follicular Large-Cell,Lymphomas, Follicular Mixed-Cell,Lymphomas, Giant Follicular,Lymphomas, Nodular,Lymphomas, Nodular Histiocytic,Mixed Cell Lymphoma, Follicular,Mixed-Cell Lymphomas, Follicular,Nodular Histiocytic Lymphoma,Nodular Histiocytic Lymphomas,Nodular Large Follicular Center Cell Lymphoma,Nodular Lymphoma,Nodular Lymphomas,Small Cleaved Cell Lymphoma, Follicular,Small Follicular Center Cell Lymphoma
D011947 Receptors, Antigen, B-Cell IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment. Antigen Receptors, B-Cell,B-Cell Antigen Receptor,B-Cell Antigen Receptors,Surface Immunoglobulin,Immunoglobulins, Membrane-Bound,Immunoglobulins, Surface,Membrane Bound Immunoglobulin,Membrane-Bound Immunoglobulins,Receptors, Antigen, B Cell,Surface Immunoglobulins,Antigen Receptor, B-Cell,Antigen Receptors, B Cell,B Cell Antigen Receptor,B Cell Antigen Receptors,Bound Immunoglobulin, Membrane,Immunoglobulin, Membrane Bound,Immunoglobulin, Surface,Immunoglobulins, Membrane Bound,Membrane Bound Immunoglobulins,Receptor, B-Cell Antigen,Receptors, B-Cell Antigen
D011993 Recombinant Fusion Proteins Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes. Fusion Proteins, Recombinant,Recombinant Chimeric Protein,Recombinant Fusion Protein,Recombinant Hybrid Protein,Chimeric Proteins, Recombinant,Hybrid Proteins, Recombinant,Recombinant Chimeric Proteins,Recombinant Hybrid Proteins,Chimeric Protein, Recombinant,Fusion Protein, Recombinant,Hybrid Protein, Recombinant,Protein, Recombinant Chimeric,Protein, Recombinant Fusion,Protein, Recombinant Hybrid,Proteins, Recombinant Chimeric,Proteins, Recombinant Fusion,Proteins, Recombinant Hybrid
D005818 Genetic Engineering Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. Genetic Intervention,Engineering, Genetic,Intervention, Genetic,Genetic Interventions,Interventions, Genetic
D006031 Glycosylation The synthetic chemistry reaction or enzymatic reaction of adding carbohydrate or glycosyl groups. GLYCOSYLTRANSFERASES carry out the enzymatic glycosylation reactions. The spontaneous, non-enzymatic attachment of reducing sugars to free amino groups in proteins, lipids, or nucleic acids is called GLYCATION (see MAILLARD REACTION). Protein Glycosylation,Glycosylation, Protein
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D016393 Lymphoma, B-Cell A group of heterogeneous lymphoid tumors generally expressing one or more B-cell antigens or representing malignant transformations of B-lymphocytes. B-Cell Lymphoma,B Cell Lymphoma,B-Cell Lymphomas,Lymphoma, B Cell,Lymphomas, B-Cell

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