Basophils FceRI

Lantz CS, Yamaguchi M, Oettgen HC, Katona IM, Miyajama I, Kinet JP, Gafii SJ. IgE regulates mouse basophil FceRI expression in vivo. J Immunol 1997 158 2517-2521. 

It is generally accepted (based on clinical and in vitro studies) that mast cells (and basophils), IgE and FceRI are involved in most cases of allergen-induced anaphylaxis in humans. However, it is difficult to define the exact roles and relative importance of mast cells, basophils, and other potential effector cells (e.g monocytes/macrophages, dendritic cells) in either IgE-dependent or IgE-independent human anaphylaxis. Unlike in mice, we neither have access to mast cell- or basophil-deficient humans nor can we genetically manipulate human subjects to produce such phenotypes. 

Hamilton RG, Lichtenstein LM Down-regulation of FceRI expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibody. J Immunol 1997 158 ... 

FceRI is a high-affinity receptor. Apart from mast cells and basophils, it may be found on Langerhans cells, eosinophils, and monocytes. 

Human basophils and mast cells are the only cells expressing the tetrameric high-affinity receptor of IgE (FceRI) and synthesizing histamine [26], Basophils and mast cells (FceRI + cells) play a prime role in the pathophysiology of allergic disorders through the elaboration and release of numerous proinflammatory and immunoregulatory molecules and the expression of a wide spectrum of receptors for cytokines and chemokines [27,28]. 

Protein Fv binds specifically to the VH domain of immunoglobulins [22], Consequently, this endogenous protein is similar to multivalent antigens or to divalent anti-IgE antibodies. To evaluate the mechanism whereby this protein activates basophils, we incubated protein Fv with human monoclonal IgM from diverse VH families [19,29], Preincubation of basophils with three preparations of human monoclonal IgM VH3+ concentration-dependently inhibited the histamine-releasing activity of protein Fv. In contrast, a monoclonal IgM that has a Vh6 domain had no such effect. These results are compatible with the hypothesis that protein Fv binds to IgE VH3 + bound to FceRI+ cells. 

Brief exposure to low pH removes most of the IgE bound to FceRI-l- cells and completely blocks the effects exerted by gpl20 and by anti-IgE on IL-4 and IL-13 secretion from basophils [55, 56]. This indicated that gpl20-induced activation of FceRI-l- cells occurs via the interaction with basophil-bound IgE [57]. Preincubation of gpl20 with human monoclonal IgM VH3 + inhibited the effect of gpl20 on cytokine secretion from basophils. In contrast, preincubation with a monoclonal IgM VH6+ had no effect. Thus, binding to the Vh3 domain prevents gpl20 interaction with IgE bound to FceRI on basophils and mast cells. 

The Vh3 family is the largest in the human cell repertoire (approx. 50%) [52, 53], therefore shed or virus-bound gpl20 could interact with high frequency with IgE Vh3 + bound to basophils of individuals at an early stage of infection. Consequently, the viral superantigen gpl20 can rapidly activate FceRI-l- cells via IgE VH3 +. 

We previously showed that protein L induces proinflammatory mediator release from human basophils and mast cells, probably by interacting with FceRI-bound IgE [72, 79], We next evaluated whether protein L and a fragment of protein L denoted B1-B4 , which comprises four of the five immunoglobulinbinding repeats [73], induce cytokine (IL-4 and IL-13) synthesis and secretion from human basophils. Protein L and B,-B4 stimulated IL-4 release from basophils [80] and there was a significant correlation between IL-4 release induced by protein L and by B,-B4. These data demonstrate that protein L induces the secretion of IL-4 and IL-13, which are important for the polarization of Th2 cells [81], from basophils. 

We also carried out a series of experiments to evaluate the mechanism of action of protein L on basophils. Brief exposure to a low pH that removes most of the IgE bound to basophils [18,55] completely blocked the effect exerted by both protein L and B,-B4 on cytokine release from basophils. We further examined the relationship between protein L and anti-IgE using cross-desensitization between the two stimuli. The IL-4 release induced by protein L or anti-IgE was greatly reduced when cells had previously been challenged with anti-IgE or protein L, respectively. Basophils desensitized with protein L or anti-IgE remained responsive to anti-FceRIa, which activates a specific epitope on the a-chain of FceRI. Consequently, we may conclude that the releasing property of protein L is mediated by interaction with IgE present on basophils. 

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