Understanding the functional heterogeneity between memory B cells expressing different immunoglobulin subclasses

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 after 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 after antibody repertoire sequencing of B cell subsets from the human tonsil. 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 a 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.