De novo gene mutations in normal human memory B cells

L. M. Slot, T. A.M. Wormhoudt, M. J. Kwakkenbos, K. Wagner, A. Ballering, A. Jongejan, A. C.M. van Kampen, J. E.J. Guikema, R. J. Bende, Carel J. M. van Noesel

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)

Abstract

In the past years, the genomes of thousands of tumors have been elucidated. To date however, our knowledge on somatic gene alterations in normal cells is very limited. In this study, we demonstrate that tetanus-specific human memory B lymphocytes carry a substantial number of somatic mutations in the coding regions of the genome. Interestingly, we observed a statistically significant correlation between the number of exome mutations and those present in the immunoglobulin heavy variable regions. Our findings indicate that the majority of these genomic mutations arise in an antigen-dependent fashion, most likely during clonal expansion in germinal centers. The knowledge that normal B cells accumulate genomic alterations outside the immunoglobulin loci during development is relevant for our understanding of the process of lymphomagenesis.

Original languageEnglish
Pages (from-to)1219-1230
Number of pages12
JournalLeukemia
Volume33
Issue number5
DOIs
Publication statusPublished - 1-May-2019
Externally publishedYes

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