Human memory B cells are highly stable while plasmablasts are recurrent

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It is known that memory B cells persist throughout life and rapidly differentiate into antibody-producing plasma cells when they encounter antigens. However, the clonal structure of memory B cells and their relationship to newly generated plasma cells are far from being understood.

By isolating circulating memory B cells and plasmablasts from two healthy adults over a period of several years and using single-cell sequencing, it was possible to define clonal families and reconstruct clonal family trees.

This study revealed three unprecedented results: it was discovered that the memory B-cell repertoire is dominated by large clonal families producing IgM, IgA and IgG2. In contrast, families producing IgG1, including those encoding antibodies to recall antigens, are smaller. The analysis demonstrated the stability of the memory B-cell pool in all its subpopulations. The continued generation of plasmablasts specifically for recall antigens such as measles virus or tetanus toxoid in the absence of recent exposure has also been demonstrated.

Overall, these results support a model in which memory B-cell activation continuously generates plasmablasts at a low rate, thus contributing to the maintenance of bone marrow plasma cells and serum antibody levels.

The study, conducted by Federica Sallusto (IRB-USI, Bellinzona and ETH Zurich) and Antonio Lanzavecchia (National Institute of Molecular Genetics, Milan, Italy) in collaboration with Humabs BioMed (subsidiary of Vir Biotechnology), was published in Nature Immunology.

Article - Clonal structure, stability and dynamics of human memory B cells and circulating plasmablasts.

Full article - ’022 -01230-1

Research briefing - ’022 -01240-z