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Switched-memory B cells remodel B cell receptors within secondary germinal centers

McHeyzer-Williams, L.J., Milpied, P.J., Okistu, S.L., McHeyzer-Williams, M.G.

Effective vaccines induce high-affinity memory B cells and durable antibody responses through accelerated mechanisms of natural selection. Secondary changes in antibody repertoires after vaccine boosts suggest progressive B cell receptor (BCR) re-diversification, but underlying mechanisms remain unresolved. Here integrated specificity and function of individual memory B cell progeny reveal ongoing evolution of polyclonal antibody specificities through germinal center (GC) specific transcriptional activity. At the clonal and sub-clonal levels, single cell expression of Cd83 and Pol□ segregates the secondary GC transcriptional program into 4 stages that regulate divergent mechanisms of memory BCR evolution. These studies demonstrate that vaccine boosts re-activate a cyclic program of GC function in switched-memory B cells to remodel existing antibody specificities and enhance durable immune protection.

Citation

McHeyzer-Williams, L.J., Milpied, P.J., Okistu, S.L., McHeyzer-Williams, M.G. "Switched-memory B cells remodel B cell receptors within secondary germinal centers" Nature Immunology (2015): 296–305