Universität zu Köln

Montesinos-Rongen, Manuel ORCID: 0000-0003-4724-5526, Terrao, Monica, May, Caroline, Marcus, Katrin, Blumcke, Ingmar, Hellmich, Martin ORCID: 0000-0001-5174-928X, Kuppers, Ralf, Brunn, Anna and Deckert, Martina (2021). The process of somatic hypermutation increases polyreactivity for central nervous system antigens in primary central nervous system lymphoma. Haematologica, 106 (3). S. 708 - 718. PAVIA: FERRATA STORTI FOUNDATION. ISSN 0390-6078

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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 naive BCR (nBCR) by reverting tBCR somatic mutations in ten PCNSL. Analysis of nBCR-derived recAb reactivity by a protein microarray and immunoprecipitation demonstrated autoand 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Montesinos-Rongen, Manuel UNSPECIFIED orcid.org/0000-0003-4724-5526 UNSPECIFIED Terrao, Monica UNSPECIFIED UNSPECIFIED UNSPECIFIED May, Caroline UNSPECIFIED UNSPECIFIED UNSPECIFIED Marcus, Katrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Blumcke, Ingmar UNSPECIFIED UNSPECIFIED UNSPECIFIED Hellmich, Martin UNSPECIFIED orcid.org/0000-0001-5174-928X UNSPECIFIED Kuppers, Ralf UNSPECIFIED UNSPECIFIED UNSPECIFIED Brunn, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Deckert, Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-592323
DOI:	10.3324/haematol.2019.242701
Journal or Publication Title:	Haematologica
Volume:	106
Number:	3
Page Range:	S. 708 - 718
Date:	2021
Publisher:	FERRATA STORTI FOUNDATION
Place of Publication:	PAVIA
ISSN:	0390-6078
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CENTER B-CELLS; AUTOANTIBODIES; ANTIBODY; MUTATION; SPECIFICITY; SEQUENCES; ABSENCE Multiple languages Hematology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59232