Germinal center–dependent and –independent memory B cells produced throughout the immune response
Charlotte Viant, Tobias Wirthmiller, Mohamed ElTanbouly, Spencer T. Chen, Ervin E. Kara, Melissa Cipolla, Víctor Ramos, Thiago Y. Oliveira, Leonidas Stamatatos, Michel C. Nussenzweig
Abstract
Memory B cells comprise a heterogenous group of cells that differ in origin and phenotype. During the early phases of the immune response, activated B cells can differentiate into IgM-expressing memory cells, short-lived plasma cells, or seed germinal centers (GCs). The memory compartment is subsequently enriched by B cells that have been through several rounds of division and selection in the GC. Here, we report on the use of an unbiased lineage-tracking approach to explore the origins and properties of memory B cell subsets in mice with an intact immune system. We find that activated B cells continue to differentiate into memory B cells throughout the immune response. When defined on the basis of their origins, the memory B cells originating from activated B cells or GCs differ in isotype and overall gene expression, somatic hypermutation, and their affinity for antigen.