The germinal centre produces memory B cells (MBCs), which upon re-activation are a key mediator of vaccine-induced immunity. However despite the importance of immunological memory, the precise mechanism by which MBCs are re-activated has not been fully elucidated. Thus, this study sought to examine the location, re-activation and differentiation of MBCs. To investigate these questions, we performed adoptive transfer studies to examine the in situ response of hen egg lysozyme (HEL)-specific SWHEL B cells in their native microenvironment in immune animals.
Utilising two-photon microscopy, we found MBCs were preferentially located in the subcapsular region of the draining lymph node where they continuously scan CD169+ subcapsular sinus macrophages for antigen in the steady state. Unexpectedly, we found that upon antigen recall, memory B cells are rapidly reactivated to proliferate and differentiate into short-lived antibody-secreting plasmablasts in this subcapsular region, in a previously unappreciated structure we have named the subcapsular proliferative foci (SPF). This SPF is a dynamic transient microanatomical compartment that is structurally and functionally distinct from the germinal centre. Thus, focused delivery of antigen and T cell help to memory B cells within the SPF explains the rapid kinetics of the secondary antibody response. Importantly, memory B cells were also shown to reside in the follicular mantle and form SPF in human lymph nodes. Targeting this evolutionarily conserved immune response pathway may be a useful strategy in future vaccine design.