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Title: Unique maturation program of the IgE response in vivo

Author
item ERAZO, AGUSTIN - NEW YORK UNIV
item KUTCHUKHIDZE, NINO - NEW YORK UNIV
item LEUNG, MONICA - NEW YORK UNIV
item GUARNIERI-CHRIST, A - UNIV DE SAN PAULO BRAZIL
item Urban, Joseph
item CUROTTO DE LAFAILLI, M - NEW YORK UNIV
item LAIFAILLE, J - NEW YORK UNIV

Submitted to: Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/15/2006
Publication Date: 2/8/2007
Citation: Erazo, A., Kutchukhidze, N., Leung, M., Guarnieri-Christ, A.P.,Urban Jr,J.F., Curotto De Lafailli, M.A., Laifaille, J.J. 2007. Unique maturation program of the IgE response in vivo. Immunity. 26(2):191-203.

Interpretive Summary: Immunity to nematode parasites is characterized by an immediate type hypersensitivity reaction that can expel worms from the intestine. The immune system reacts to parasitic worms by the production of a relatively minor class of antibodies called IgE antibody that is specific for parasite antigens and binds to particular effector cells. These cells contain pharmacologically active agents that when released from the cell after binding of parasite antigen to surface IgE will contribute to the tissue response that regulate worm expulsion. The development of cells that produce IgE antibodies is understood as a sequence of gene rearrangements, but it is not clear where in the lymph nodes these events take place or if these cells have distinguishing characteristics from other antibody producing cells. This study shows that defined antigens immunized into mice with preparations that stimulate IgE antibody production as well as inoculation of mice with a nematode parasite will stimulate development of IgE containing cells in distinct regions of the lymph node. In addition, selective markers of cell development are detected to distinguish these cells as IgE producers. These results will aid in the induction and detection of IgE producing cells that can contribute to a better understanding of how to facilitate protective responses to parasitic infection. Scientists interested in these infectious agents and control of protective responses will benefit from this information.

Technical Abstract: A key event in the pathogenesis of asthma and allergies is the production of IgE antibodies. We show here that IgE+ cells are exceptional because they are largely found outside germinal centers and express, from very early on, a genetic program of plasma cells. In spite of their extra-germinal center localization, IgE+ cells show signs of somatic hyper-mutation and affinity maturation. We show here that high-affinity IgE+ cells are generated through a unique differentiation program that involves two phases: a pre-IgE phase in which somatic hyper-mutation and affinity maturation take place in IgG1+ cells, and a post-IgE-switching phase in which IgE cells differentiate swiftly into plasma cells. Our results have implications for the understanding of IgE memory responses in allergy.