Clonal structure and dynamics of human memory B cells and circulating plasmablasts

Using single cell sequencing of multi-year serial blood samples from two healthy donors we found that the memory B cell repertoire was dominated by large clonal families producing IgM, IgG2 and IgA, of which 0.2% share nearly identical VH/VL sequences in different individuals. In contrast, IgG1 families, including those encoding antibodies to T-dependent antigens, were of small size. Longitudinal samples collected over a period of several years showed the overall stability of the memory B cell pool in all its subsets. Surprisingly, clonotype stability was also found in serial samples of circulating plasma cells that largely overlapped with long-term memory B cells and contained recurrent clonotypes of IgA and IgG2 and, at lower frequency, IgG1 specific for recall antigens. Collectively, this study provides a global view of the structure, stability and dynamics of the human memory B cell pool and reveal that a large fraction of the clonal families is active at any time point in the generation of plasma cells involving both T independent and T dependent responses. Single cell immune profiling (gene expression) of plasma cells from healthy human donor