The studies described in this thesis help understand why disturbances in specific genes and processes lead to antibody deficiencies. They showed that B cell precursor development in bone marrow is not a simple linear process, but rather a complex interplay of processes that make every individual cell follow its own route of maturation into a naive B cell. Furthermore, these studies showed that subtle differences in protein function can explain phenotypical differences between different disease entities in CD19- complex deficiencies. Showing how genotype-phenotype correlations can be a tool in patient-prognostics. These studies also showed that the balance in the PI3K/PTEN-AKT signaling cascade is critically important for both humoral and anti-viral immunity, since disturbances lead to antibody deficiencies and reduced viral immunity due to exhaustion. This is especially important in the context of new, personalized, specific treatments for these patients.

primary antibody deficiencies, B cells, B cell differentiation, bone marrow
J.J.M. van Dongen (Jacques) , M. van der Burg (Mirjam)
Erasmus University Rotterdam
Postgraduate School Molecular Medicine (MM)

Wentink, M.W.J. (2018, July 4). Connecting B cell differentiation pathways and antibody deficiencies. Erasmus University Rotterdam. Retrieved from