title: Primary Central Nervous System (CNS) Lymphoma B Cell Receptors Recognize CNS Proteins.
abstract: Primary lymphoma of the CNS (PCNSL) is a diffuse large B cell lymphoma confined to the CNS. To elucidate its peculiar organ tropism, we generated recombinant Abs (recAbs) identical to the BCR of 23 PCNSLs from immunocompetent patients. Although none of the recAbs showed self-reactivity upon testing with common autoantigens, they recognized 1547 proteins present on a large-scale protein microarray, indicating polyreactivity. Interestingly, proteins (GRINL1A, centaurin-α, BAIAP2) recognized by the recAbs are physiologically expressed by CNS neurons. Furthermore, 87% (20/23) of the recAbs, including all Abs derived from IGHV4-34 using PCNSL, recognized galectin-3, which was upregulated on microglia/macrophages, astrocytes, and cerebral endothelial cells upon CNS invasion by PCNSL. Thus, PCNSL Ig may recognize CNS proteins as self-Ags. Their interaction may contribute to BCR signaling with sustained NF-κB activation and, ultimately, may foster tumor cell proliferation and survival. These data may also explain, at least in part, the affinity of PCNSL cells for the CNS.
authors.affiliation: Institute of Neuropathology, University Hospital of Cologne, D-50925 Cologne, Germany; and.
authors.forename: Manuel
authors.initials: M
authors.lastname: Montesinos-Rongen
authors.affiliation: Institute of Neuropathology, University Hospital of Cologne, D-50925 Cologne, Germany; and.
authors.forename: Frauke G
authors.initials: FG
authors.lastname: Purschke
authors.affiliation: Institute of Neuropathology, University Hospital of Cologne, D-50925 Cologne, Germany; and.
authors.forename: Anna
authors.initials: A
authors.lastname: Brunn
authors.affiliation: Medical Proteome-Center, Ruhr-University Bochum, D-44801 Bochum, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: May
authors.affiliation: Medical Proteome-Center, Ruhr-University Bochum, D-44801 Bochum, Germany.
authors.forename: Eckhard
authors.initials: E
authors.lastname: Nordhoff
authors.affiliation: Medical Proteome-Center, Ruhr-University Bochum, D-44801 Bochum, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Marcus
authors.affiliation: Institute of Neuropathology, University Hospital of Cologne, D-50925 Cologne, Germany; and martina.deckert@uni-koeln.de.
authors.forename: Martina
authors.initials: M
authors.lastname: Deckert
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000912:Antibodies, Neoplasm / Q000276:immunology*; D001253:Astrocytes / Q000276:immunology; D001483:Base Sequence; D001798:Blood Proteins; D018287:Carcinoma, Large Cell / Q000276:immunology; D049109:Cell Proliferation; D016543:Central Nervous System Neoplasms / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology; D004789:Enzyme Activation; D005260:Female; D037502:Galectin 3 / Q000276:immunology; D037161:Galectins; D020869:Gene Expression Profiling; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000276:immunology; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D017628:Microglia / Q000276:immunology; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000276:immunology; D012319:RNA Polymerase II / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D017422:Sequence Analysis, DNA
chemical_list: C100956:ADAP1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D000912:Antibodies, Neoplasm; C119539:BAIAP2 protein, human; D001798:Blood Proteins; D037502:Galectin 3; D037161:Galectins; C014609:IgK; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007136:Immunoglobulins; C428445:LGALS3 protein, human; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; C433812:POLR2M protein, human; D011947:Receptors, Antigen, B-Cell; D012319:RNA Polymerase II