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

Manuel Montesinos-Rongen; Frauke G Purschke; Anna Brunn; Caroline May; Eckhard Nordhoff; Katrin Marcus; Martina Deckert

doi:10.4049/jimmunol.1402341

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.

Authors

Manuel Montesinos-Rongen¹, Frauke G Purschke¹, Anna Brunn¹, Caroline May², Eckhard Nordhoff², Katrin Marcus², Martina Deckert³

Affiliations

¹ Institute of Neuropathology, University Hospital of Cologne, D-50925 Cologne, Germany; and.
² Medical Proteome-Center, Ruhr-University Bochum, D-44801 Bochum, Germany.
³ Institute of Neuropathology, University Hospital of Cologne, D-50925 Cologne, Germany; and martina.deckert@uni-koeln.de.

PMID: 26116512
DOI: 10.4049/jimmunol.1402341

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
Blood Proteins
Carcinoma, Large Cell / immunology
Cell Proliferation
Central Nervous System Neoplasms / immunology*
Endothelial Cells / immunology
Enzyme Activation
Female
Galectin 3 / immunology
Galectins
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
Blood Proteins
Galectin 3
Galectins
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