Memory B-cell persistence is independent of persisting immunizing antigen

Immunological memory in the antibody system is generated in T-cell-dependent responses and carried by long-lived memory B cells that recognize antigen by high-affinity antibodies(1,2). But it remains controversial(1) whether these B cells represent true 'memory' cells (that is, their maintenance is independent of the immunizing antigen), or whether they are a product of a chronic immune response driven by the immunizing antigen, which can be retained in the organism for extended time periods on the surface of specialized antigen-presenting cells (follicular dendritic cells)(3). Cell transfer experiments provided evidence in favour of a role of the immunizing antigen(4,5); however, analysis of memory cells in intact animals, which showed that these cells are mostly resting(6) and can persist in the absence of detectable T-cell help(7) or follicular dendritic cells(8), argued against it. Here we show, by using a genetic switch mediated by Cre recombinase, that memory B cells switching their antibody specificity away from the immunizing antigen are indeed maintained in the animal over long periods of time, similar to cells retaining their original antigen-binding specificity.