Understanding the functional heterogeneity between memory B cells expressing different immunoglobulin subclasses (360G-Wellcome-208961_Z_17_Z)

The quality of the antibody response to different antigens in distinct microenvironments is determined by the functional properties of specific B cells. Evidence suggests that B cells expressing different antibody subclasses display functional heterogeneity that could influence their ability to expand, migrate and differentiate following activation. This study will test the hypothesis that human memory B cells expressing different antibody subclasses are functionally distinct. Rates of clonal diversification (expansion, class-switching, somatic hypermutation and differentiation) by B cells expressing different antibody subclasses will be compared following antibody repertoire sequencing of human tonsil B cell subsets. In addition, the functional diversity of human class-switched B cells will be assessed by single-cell RNA sequencing. B cell subtypes will be classified using gene-expression-based clustering and the distribution of B cells expressing different antibody subclasses across different clusters will be calculated. Identification of genes and gene-related pathways that define functionally distinct B cell subtypes would lead to more precise understanding of how B cell memory is generated. This would inform approaches that aim to promote or suppress specific antibody responses and would provide a basis for examining mechanisms that drive dysregulation of B cell memory in human disease. Keywords: B cells, antibody, immunology, immune memory