The process of somatic hypermutation increases polyreactivity for central nervous system antigens in primary central nervous system lymphoma

Montesinos-Rongen M, Terrao M, May C, Marcus K, Blümcke I, Hellmich M, Kuppers R, Brunn A, Deckert M (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Haematologica Ferrata Storti Foundation

Book Volume: 106

Pages Range: 708-717

Journal Issue: 3

DOI: 10.3324/haematol.2019.242701

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.

Authors with CRIS profile

Ingmar Blümcke Lehrstuhl für Neuropathologie

Involved external institutions

Ruhr-Universität Bochum (RUB) DE Germany (DE) Universität Duisburg-Essen (UDE) DE Germany (DE) Universität zu Köln DE Germany (DE)

How to cite

APA:

Montesinos-Rongen, M., Terrao, M., May, C., Marcus, K., Blümcke, I., Hellmich, M.,... Deckert, M. (2021). The process of somatic hypermutation increases polyreactivity for central nervous system antigens in primary central nervous system lymphoma. Haematologica, 106(3), 708-717. https://doi.org/10.3324/haematol.2019.242701

MLA:

Montesinos-Rongen, Manuel, et al. "The process of somatic hypermutation increases polyreactivity for central nervous system antigens in primary central nervous system lymphoma." Haematologica 106.3 (2021): 708-717.

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