Chronic Malaria drives functional heterogenity in B cell subpopulations and expansion of unswitched atypical memory B cells [Malaria bulkRNA-seq]

Human chronic infectious diseases have been shown to alter the composition and phenotype of the B cell compartment, which, in part, can attribute to failure to acquire protective immunity. However, the extent of such alterations is poorly understood. Here, using a combination of bulk and single cell RNA-sequencing (scRNA-seq) of B cells in individuals living in malaria-endemic Africa, we characterized changes in naïve B cell, classical memory B cell (MBC) and atypical MBC subsets. Of particular interest were unswitched atypical MBCs that expanded in children upon the onset of febrile malaria. This subpopulation expressed IgD but only low levels of IgM (IgD+IgMlo), high levels of the atypical MBC markers, Tbet and CD11c, as well as the intrinsically autoreactive VH4-34. IgD+IgMlo atypical MBCs were distinguished functionally by their acquisition of high antigen-affinity thresholds for activation, suggesting the IgD+IgMlo atypical MBC expansion during febrile malaria may reduce responses to low affinity self-antigens during acute malaria Differential gene expression between four B cell subsets - Naïve B cells (CD21+CD27-), classical memory B cell (CMBC- CD21+CD27+), activated memroy B cell (AcMBC- CD21-CD27+) and atypical MBC (CD21-CD27-) obtained by sorting peripheral blood B cells (CD19+CD20+CD10-) of three adults living in Malaria-endemic Mali The raw data is to be made available through dbGaP (controlled access; phsnnnnnn)