TO E OR NOT TO E - CAN AND IL-4-INDUCED B-CELL CHOOSE BETWEEN IGE ANDIGG4

Parasite immunologists had known for some time that IgE-mediated hyper sensitivity reactions are rare in patients with chronic helminth infec tions, even though basophils and mast cells in these patients are sens itized with antiparasite IgE and exposed, often continuously, to paras ite antigens. The inhibition of allergic reactivity in chronic helmint h infections is mainly due to IgG4 'blocking antibodies' in the serum of the infected individual. IgG4 do not fix complement and bind weakly to Fc gamma receptors. Thus, antigen binding by IgG4, unlike IgE, is likely to have no or minimally harmful consequences. The discovery tha t, similar to IgE, expression of IgG4 is IL-4-dependent and is an inte rmediate step in sequential switching from IgM to IgE makes it imperat ive to understand how the two isotypes are coregulated and whether the two responses can be uncoupled, selectively boosting IgG4 over IgE. T he ultimate goal is to apply to allergy the lesson we learnt from helm inth infections.