Memory B-cell persistence is independent of persisting immunizing antigen

Immunological memory in the antibody system is generated in T-cell-dependen t 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 reta ined in the organism for extended time periods on the surface of specialize d antigen-presenting cells (follicular dendritic cells)(3). Cell transfer e xperiments provided evidence in favour of a role of the immunizing antigen( 4,5); however, analysis of memory cells in intact animals, which showed tha t these cells are mostly resting(6) and can persist in the absence of detec table T-cell help(7) or follicular dendritic cells(8), argued against it. H ere we show, by using a genetic switch mediated by Cre recombinase, that me mory B cells switching their antibody specificity away from the immunizing antigen are indeed maintained in the animal over long periods of time, simi lar to cells retaining their original antigen-binding specificity.