Constrained by the absence of somatic hypermutation(SHM) in follicular mantle B cells, FM-Tfh could only induce IgE+B cells, without generating autoreactive IgE antibodies (60), and eventually induce low affinity IgE, which play a role in allergy, due to their rapid antibody generation and reaction, for example, IL-9R+FM-Tfh drive five-fold increases in house dust mite (HDM)-specific IgE, with IL-9R blockade significantly ameliorating allergic responses (79). This evidence concerns the gene IGHE and allergic disease.