Lifelong memory responses perpetuate humoral T(H)2 immunity and anaphylaxis in food allergy.
Lifelong memory responses perpetuate humoral T(H)2 immunity and anaphylaxis in food allergy.
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DOI：
10.1016/j.jaci.2017.01.018
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发表时间：
2017-12
期刊：
影响因子：
--
通讯作者：
Jordana M
中科院分区：
文献类型：
--
作者：
Jiménez-Saiz R;Chu DK;Mandur TS;Walker TD;Gordon ME;Chaudhary R;Koenig J;Saliba S;Galipeau HJ;Utley A;King IL;Lee K;Ettinger R;Waserman S;Kolbeck R;Jordana M
A number of food allergies (e.g. fish, shellfish, nuts) are lifelong, without any disease-transforming therapies and unclear in their underlying immunology. Clinical manifestations of food allergy are largely mediated by IgE. Although persistent IgE titres have conventionally been attributed to long-lived IgE+ plasma cells (PCs), this has not been directly and comprehensively tested. To evaluate mechanisms underlying persistent IgE and allergic responses to food allergens. We used a model of peanut allergy and anaphylaxis, various knockout mice, adoptive transfer experiments and in vitro assays, to identify mechanisms underlying persistent IgE humoral immunity over almost the entire life-span of the mouse (18-20 months). Contrary to conventional paradigms, our data show that clinically relevant lifelong IgE titres are not sustained by long-lived IgE+ PCs. Instead, lifelong reactivity is conferred by allergen-specific long-lived memory B cells that replenish the IgE+ PC compartment. B cell re-activation requires allergen re-exposure and IL-4 production by CD4 T cells. We define the half-lives of antigen-specific: germinal centers (23.3 days); IgE+ and IgG1+ PCs (60 days and 234.4 days respectively) and clinically-relevant cell-bound IgE (67.3 days). These findings can explain lifelong food allergies observed in humans as the consequence of allergen exposures that recurrently activate memory B cells and identify these as a therapeutic target with disease-transforming potential. R. Jimenez-Saiz and D.K. Chu et al. examine lifelong IgE responses in food allergy and identify that allergen-specific long-lived memory B-cells and IL-4 producing CD4 T cells are critical to this process by re-generating reservoirs of IgE-secreting plasma cells.
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影响因子：
4.3
作者：
HARUNA, K;HIKIDA, M;OHMORI, H
通讯作者：
OHMORI, H
影响因子：
158.5
作者：
Leung, DYM;Sampson, HA;Shanahan, WR
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Shanahan, WR
影响因子：
30.5
作者：
Dogan, Ismail;Bertocci, Barbara;Weill, Jean-Claude
通讯作者：
Weill, Jean-Claude
影响因子：
12.4
作者：
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通讯作者：
Jordana, M.
影响因子：
14.2
作者：
Berkowska, Magdalena A.;Heeringa, Jorn J.;van Zelm, Menno C.
通讯作者：
van Zelm, Menno C.