Secreted IgD Amplifies Humoral T Helper 2 Cell Responses by Binding Basophils via Galectin-9 and CD44

Abstract

Summary B cells thwart antigenic aggressions by releasing immunoglobulin M (IgM), IgG, IgA and IgE, which deploy well-understood effector functions. In contrast, the role of secreted IgD remains mysterious. We found that some B cells generated IgD-secreting plasma cells following early exposure to external soluble antigens such as food proteins. Secreted IgD targeted basophils by interacting with the CD44-binding protein galectin-9. When engaged by antigen, basophil-bound IgD incresed basophil secretion of interleukin-4 (IL-4), IL-5 and IL-13, which facilitated the generation of T follicular helper type-2 cells expressing IL-4. These germinal center T cells enhanced IgG1 and IgE but not IgG2a and IgG2b responses to the antigen initially recognized by basophil-bound IgD. In addition, IgD ligation by antigen attenuated allergic basophil degranulation induced by IgE co-ligation. Thus, IgD may link B cells with basophils to optimize humoral T helper type-2-mediated immunity against common environmental soluble antigens.

Sustained successful peanut oral immunotherapy associated with low basophil activation and peanut-specific IgE

“…Furthermore, other immunoglobulin isotypes induced by OIT can potentially inhibit basophil activation. 45,46 It is conceivable that peanut immunotherapy induces immunologic modifications (such as reduction in peanut sIgE and increase in peanut sIgG, sIgA, and sIgD), which in turn alter basophil phenotype (such as reduction of FcεR, Syk, 47 and other intracellular signaling machinery) and thus reduces basophil responsiveness to food allergens, and clinical reactivity. Therefore, we think that BATs ideally should be performed in whole blood, as we did in this study, to evaluate OIT-induced immune modifications external to basophils, as well as intrinsic changes in basophils.…”

Allergen‐specific immunotherapy boosts allergen‐specific IgD production in house dust mite‐sensitized asthmatic patients

“…The hypothesis that as high is the pretreatment eosinophil count, as better would be the clinical response, was apparently confirmed in the phase III regulatory trials. [2][3][4] In this context, it must be considered that the patients enrolled in the phase III trials are different from those treated in the real-life context. 5 In this analysis, we attempted to correlate the baseline EOS count with the clinical, functional, and biological outcome changes, and to assess whether baseline EOS could be a predictive biological marker.…”

Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

“…A population of IgM – IgD + class switched B cell has been reported. These cells are primarily found in secondary lymphoid organs and are not readily detected in peripheral blood .…”