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 analyzed the regulation of AID in AID reporter mice. ? 1- By fusing to the AID gene fluorescent molecules (such as the green fluorescent protein (GFP) isolated from the jellyfish Aequorea victoria), we were able to visualize B cells (green fluorescent cells) activated during infection or immunization. ? 2- We also 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 tool is allowing us to study 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.

Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2006
Total Cost
Indirect Cost
Name
Arthritis, Musculoskeletal, Skin Dis
Department
Type
DUNS #
City
State
Country
United States
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Teng, Grace; Hakimpour, Paul; Landgraf, Pablo et al. (2008) MicroRNA-155 is a negative regulator of activation-induced cytidine deaminase. Immunity 28:621-9
Takizawa, Makiko; Tolarova, Helena; Li, Zhiyu et al. (2008) AID expression levels determine the extent of cMyc oncogenic translocations and the incidence of B cell tumor development. J Exp Med 205:1949-57
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Casellas, Rafael; Zhang, Qingzhao; Zheng, Nai-Ying et al. (2007) Igkappa allelic inclusion is a consequence of receptor editing. J Exp Med 204:153-60
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