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J Immunol. 2015 Aug 1;195(3):1312-9. doi: 10.4049/jimmunol.1402341. Epub 2015 Jun 26.

Primary Central Nervous System (CNS) Lymphoma B Cell Receptors Recognize CNS Proteins.

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  • 1Institute of Neuropathology, University Hospital of Cologne, D-50925 Cologne, Germany; and.
  • 2Medical Proteome-Center, Ruhr-University Bochum, D-44801 Bochum, Germany.
  • 3Institute of Neuropathology, University Hospital of Cologne, D-50925 Cologne, Germany; and


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.

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