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The process of somatic hypermutation increases polyreactivity for central nervous system antigens in primary central nervous system lymphoma
- Source :
- Haematologica
- Publication Year :
- 2020
- Publisher :
- Fondazione Ferrata Storti, 2020.
-
Abstract
- The immunoglobulin (Ig) heavy and light chain variable gene mutational pattern of the B-cell receptor (BCR) in primary central nervous system lymphoma (PCNSL) cells suggests antigenic selection to drive pathogenesis and confinement to the central nervous system (CNS). This hypothesis is supported by the observation that the tumor B-cell receptor (tBCR) of PCNSL is polyreactive and may be stimulated by CNS proteins. To obtain further insight into the role of the germinal center (GC) reaction on BCR reactivity, we constructed recombinant antibodies (recAb) with Ig heavy and light chain sequences of the corresponding naïve BCR (nBCR) by reverting tBCR somatic mutations in ten PCNSL. Analysis of nBCR-derived recAb reactivity by a protein microarray and immunoprecipitation demonstrated auto- and polyreactivity in all cases. Self- /polyreactivity was not lost during the GC reaction; surprisingly, tBCR significantly increased self-/polyreactivity. In addition to proteins recognized by both the nBCR and tBCR, tBCR gained self-/polyreactivity particularly for proteins expressed in the CNS including proteins of oligodendrocytes/ myelin, the S100 protein family, and splicing factors. Thus, in PCNSL pathogenesis, a faulty GC reaction may increase self-/polyreactivity, hereby facilitating BCR signaling via multiple CNS antigens, and may ultimately foster tumor cell survival in the CNS.
- Subjects :
- Central Nervous System
B-cell receptor
Medizin
Somatic hypermutation
Receptors, Antigen, B-Cell
Biology
Immunoglobulin light chain
Article
Central Nervous System Neoplasms
03 medical and health sciences
Myelin
0302 clinical medicine
hemic and lymphatic diseases
medicine
Humans
030304 developmental biology
0303 health sciences
Primary central nervous system lymphoma
breakpoint cluster region
Germinal center
Hematology
medicine.disease
Germinal Center
medicine.anatomical_structure
030220 oncology & carcinogenesis
Cancer research
biology.protein
Antibody
Immunoglobulin Heavy Chains
Subjects
Details
- Language :
- English
- ISSN :
- 15928721 and 03906078
- Volume :
- 106
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Haematologica
- Accession number :
- edsair.doi.dedup.....23177afaef86924efb26ea493f9bfc03