Analyzing the impact of epigenetic mechanisms on immunoglobulin class switching in neonatal B cells

• Applicant: Professorin Dr. Almut Meyer-Bahlburg
• Subject Area: Pediatric and Adolescent Medicine
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 466917762

The neonatal period is characterized by an increased susceptibility to infections. This is caused by both qualitative and quantitative differences between the neonatal and adult immune system. In regard to the B cell compartment, several differences have been described so far: The neonatal B cell compartment mainly exists of immature, so-called transitional B cells and only few mature B cells. Moreover, studies in both the human and murine system have demonstrated disturbed antibody responses to T cell dependent and independent antigens. However, the mechanisms causing this immaturity within the B cell compartment are barely understood.In previous studies, we have shown that neonatal B cells have a partial defect in immunoglobulin class switching. This was associated with an increased expression of miR-181b, a mircoRNA that has been suggested to play an important role in class switching. In the current proposal we therefore want to analyze the impact of increased miR-181b expression on immunoglobulin class switching in neonatal B cells.First, using a clearly defined mouse model, we will compare the transcriptome and proteome of B cells in miR-181a/b knock-out and heterozygous mice. Next, the identified gene products will be analyzed in human neonatal B cells from cord blood and adult B cells from peripheral blood. We will also compare signal transduction in human neonatal and adult B cell subpopulations. To directly test the impact of identified gene products and proteins on immunoglobulin class switching we will use inhibitors to block their function in stimulated B cells in vitro.In another part of the project we will also investigate B cells of preterm neonates to determine if the immaturity of these B cells is even more pronounced in comparison to B cells from mature neonates. Results from this project will contribute to a better understanding of immunoglobulin class switching in neonatal and adult B cells. This knowledge can help to improve vaccination strategies in infants.

• DFG Programme: Research Grants