B lymphocytes are the immune system cells that recognize and dispose pathogens such as viruses and bacteria though special receptors on their cell surface known as antibodies. Both pathogen recognition and disposal are facilitated by two processes known as hypermutation and switching, which are carried out by a novel protein: AID. This year we have created three genetically modified mice to study the expression of this exciting molecule. 1- By fusing to the AID gene fluorescent molecules (such as the green fluorescent protein (GFP) isolated from the jellyfish Aequorea victoria), we are able to visualize B cells (green fluorescent cells) activated during infection or immunization. 2- We have introduced the human version of AID in mice by means of a transgene. Human AID can be visualized by histology with a very specific monoclonal antibody. This technique is allowing us to pinpoint the migration of activated B cells from their first encounter with antigen (or pathogen) until they become fully differentiated (memory or plasma cells) where AID is turned off. 3- To follow the progeny of cells that have expressed AID during development but subsequently turned its expression off, we have devised a method that permanently tags activated B cells with the yellow fluorescent molecule (a GFP variant). This tools permits the study of the memory response. Memory B cells, in contrast to naive ones, become rapidly activated upon interaction with previously encountered viruses or bacteria, and explain why we do not succumb to the same infection twice.
