PhD defence A.F. (Alice) Muggen

In this thesis we studied the B cell populations and BCR repertoire of healthy individuals upon aging. We detected a decline in both absolute numbers and proportions of transitional B cells, total memory B cells, and plasma blasts in elderly, and noticed signs of increased proportions of chronically activated CD5+CD43+ B cells and CD21low B cells. Furthermore, we observed that CLL-associated stereotypic BCR are present in the normal BCR repertoire from healthy individuals and their usage appeared to increase with age. Both immunogenetic and chromosomal similarities were detected within the three CLL families in a disease that is known to be quite heterogeneous. Immunogenetically, these families represent three known CLL subgroups being M-CLL (family 1), U-CLL (family 2), and CLL#2-like CLL (family 3). Common chromosomal aberrations having prognostic value in CLL, were found to be present in these families. Deletion of 11q14.2-11q14.3 was found in family 1 and family 3 members, while trisomy 12 was detected in family 2 members. Finally, when evaluating basal Ca2+ levels we noted clear differences in BCR signaling in CLL patients compared with B cells of healthy individuals, especially upon BCR stimulation. We identified a relationship between the basal Ca2+ level and SHM status, with the Ca2+ level being higher in M-CLL. Furthermore, we observed striking differences in expression levels of several BCR signaling molecules as well as NF-κB-related genes between IgM-responsive and IgM-unresponsive CLL cases.

The public defence will take place at the Prof. Andries Queridoroom, 3rd floor Education Center, Erasmus MC. The ceremony will begin exactly at 13.30 hrs. In light of the solemn nature of the ceremony, we recommend that you do not take children under the age of 6 to the first part of the ceremony.