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Publication : Class-switched memory B cells remodel BCRs within secondary germinal centers.

First Author  McHeyzer-Williams LJ Year  2015
Journal  Nat Immunol Volume  16
Issue  3 Pages  296-305
PubMed ID  25642821 Mgi Jnum  J:259148
Mgi Id  MGI:6142365 Doi  10.1038/ni.3095
Citation  McHeyzer-Williams LJ, et al. (2015) Class-switched memory B cells remodel BCRs within secondary germinal centers. Nat Immunol 16(3):296-305
abstractText  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 rediversification of B cell receptors (BCRs), but the underlying mechanisms remain unresolved. Here, the integrated specificity and function of individual memory B cell progeny revealed ongoing evolution of polyclonal antibody specificities through germinal center (GC)-specific transcriptional activity. At the clonal and subclonal levels, single-cell expression of the genes encoding the costimulatory molecule CD83 and the DNA polymerase Poleta segregated the secondary GC transcriptional program into four stages that regulated divergent mechanisms of memory BCR evolution. Our studies demonstrate that vaccine boosts reactivate a cyclic program of GC function in class-switched memory B cells to remodel existing antibody specificities and enhance durable immunological protection.
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