It is known that memory B cells persist throughout life and rapidly differentiate into antibody-producing plasma cells upon antigen encounter. 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 recently generated 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 novel findings: 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 also showed the stability of the memory B-cell pool in all its subpopulations. The continued generation of plasmablasts specific for recall antigens such as measles virus or tetanus toxoid in the absence of recent exposure was also demonstrated.
Overall, these results support a model in which activation of memory B cells continuously generates plasmablasts at a low rate, thus contributing to the maintenance of bone marrow plasma cells and serum antibody levels.
The study led by Federica Sallusto (IRB, USI e ETH) and Antonio Lanzavecchia (National Institute of Molecular Genetics, Italy), and performed in collaboration with Humabs BioMed, a subsidiary of Vir Biotechnology has been published in Nature Immunology.
Article
Clonal structure, stability and dynamics of human memory B cells and circulating plasmablasts.
Phad, G. E., D. Pinto, M. Foglierini, M. Akhmedov, R. L. Rossi, E. Malvicini, A. Cassotta, C. S. Fregni, L. Bruno, F. Sallusto and A. Lanzavecchia
Nat Immunol. 2022; 23: 1-10.
Full article – https://www.nature.com/articles/s41590-022-01230-1
Research briefing – https://www.nature.com/articles/s41590-022-01240-z
a, Honeycomb plot showing all memory B cells (MBCs) from one donor (D1) separated into clonal families. X, isotype not determined. b, Size distribution of memory B cell families specific for different recall antigens, including measles virus (MV), respiratory syncytial virus (RSV), tetanus toxoid (TT) and influenza virus (FLU). c, Projection of circulating plasmablast families identified in 2020 (X) onto memory B cell families from 2010 (Y) from donor 1. Shared families (D) are green; unshared families are red and blue. d, Number and frequency of the shared families in c. e, Venn diagram of recurrent plasmablast families shared by different time points. © 2022, Phad, G. E. et al
