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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / immunology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Neoplasm / immunology*
  • Astrocytes / immunology
  • Base Sequence
  • Carcinoma, Large Cell / immunology
  • Cell Proliferation
  • Central Nervous System Neoplasms / immunology*
  • Endothelial Cells / immunology
  • Enzyme Activation
  • Female
  • Galectin 3 / immunology
  • Gene Expression Profiling
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Heavy Chains / immunology
  • Immunoglobulin Light Chains / genetics
  • Immunoglobulin Light Chains / immunology
  • Immunoglobulins / genetics
  • Immunoglobulins / immunology
  • Lymphoma, B-Cell / immunology*
  • Macrophages / immunology
  • Male
  • Microglia / immunology
  • Middle Aged
  • NF-kappa B / metabolism
  • Nerve Tissue Proteins / immunology
  • RNA Polymerase II / immunology
  • Receptors, Antigen, B-Cell / immunology*
  • Sequence Analysis, DNA

Substances

  • ADAP1 protein, human
  • Adaptor Proteins, Signal Transducing
  • Antibodies, Neoplasm
  • BAIAP2 protein, human
  • Galectin 3
  • IgK
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Light Chains
  • Immunoglobulins
  • LGALS3 protein, human
  • NF-kappa B
  • Nerve Tissue Proteins
  • POLR2M protein, human
  • Receptors, Antigen, B-Cell
  • RNA Polymerase II

Associated data

  • GEO/GSE61556