PhD defence
Mutagenic mechanisms in normal and neoplastic B cells: From AID- induced diversification to genome-wide patterns
- J.H. Sepulveda Yañez
- Date
- Tuesday 12 November 2024
- Time
- Location
-
Academy Building
Rapenburg 73
2311 GJ Leiden
Supervisor(s)
- Prof.dr. J.H. Veelken
- Prof.dr. M.A. Navarrete
Summary
B cells are a type of white blood cell that produce antibodies to fight infections. B cells can change the DNA of their antibodies to recognize new infections. This process is called somatic hypermutation (SHM) and is essential for the immune system to work properly. In this thesis, we studied how B cells change their DNA throughout their developmental journey. We found that B cells can change two or more DNA letters at the same time, a process called tandem mutation. We also found that B cells can change their DNA in a single step, a process called concurrent mutation.
We also studied how B cells alter their DNA in patients with hematological malignancies. We identified distinct mutational patterns associated with specific disease types. Additionally, we found that some patients with a pre-cancerous condition called monoclonal B-cell lymphocytosis (MBL) have changes in their DNA that are similar to patients with leukemia. We also studied autonomous BCR signaling, a unique mechanism in B cells that is already present in MBL patients. Understanding this mechanism helps explain the genetic and signaling dynamics behind disease progression.
This thesis provides new insights into the mechanisms of somatic hypermutation in B cells and how these mechanisms are altered in hematological malignancies.
PhD dissertations
Approximately one week after the defence, PhD dissertations by Leiden PhD students are available digitally through the Leiden Repository, that offers free access to these PhD dissertations. Please note that in some cases a dissertation may be under embargo temporarily and access to its full-text version will only be granted later.
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