Complement-regulated Homeostatic Proliferation Controls Memory B Cell Longevity and Repertoire Composition

As decay-accelerating factor (DAF, CD55), a negative regulator of complement activation, is requisitely downregulated on germinal center B cells and is re-expressed on Bmem, we investigated the effects of deleting DAF on murine (B1-8hi) Bmem in competitive settings. Kinetic analysis showed a progressive reduction in DAF-/- Bmem numbers over six weeks, without affecting Bmem production, pool size, or their ability to respond to rechallenge.

Following transfer into unimmunized hosts, wild-type Bmem proliferated to maintain stable Bmem pool sizes, outcompeting DAF-/- Bmem, reflecting homeostatic proliferation. Reduced proliferation and increased cell death in DAF-/- Bmem associated with transcriptional differences in metabolism and migration pathways. Wild type Bmem proliferation increased in C3-/- hosts, and vaccination with a heterologous antigen, which induces local complement activation, locally inhibited bystander B1-8hi Bmem proliferation.