Högskolan i Skövde

The adaptive arm of the immune system protects from reinfection and is recognized by an immense diversity of cells that interact and coevolve as novel pathogens emerge. At gestation, the mother undergoes profound and complex changes of her immune system to maintain tolerance towards the fetus while providing proper protection against any intruders. Understanding the mechanisms behind this balancing act can help identify the hallmarks of pregnancy well-being and adverse outcomes. Here, the aim was to explore the dynamic changes at gestation and after delivery in sorted B cell populations including naïve and two memory B cell (MBC) subsets named herein CD27^dull and CD27^bright from three pregnant females. The subsets were analyzed using Illumina MiSeq HTS data derived from the full-length immunoglobulin heavy chain variable region transcript incorporated with unique molecular identifiers (UMIs). The data was processed using UMI-guided error corrections and reads with shared sequence identities were assembled into clonotypes. The samples were further analyzed by comparing baseline B cell repertoire properties including variable gene segment usage (IGHV), complementarity determining region 3 (CDR3) sizes and levels of somatic hypermutations (SHMs). The results revealed a dynamic change in IGHV usage profiles and an increase of CDR3 sizes between gestation and after delivery. CD27^bright exhibited higher levels of SHMs than CD27^dull, and SHMs tend to accumulate unequally across the region. CD27^bright increased their replacement-to-silent SHM ratio after delivery. The results shed more light on maternal immune adaptation and provide a framework that can be refined and optimized in future works.