However, there are also evidence that Tph2 expand in allergic disease, secreting IL-5, IL-13, IL-21, likely to induce IgE-producing B cells (45, 112), different from that in autoimmunity (131), thus Tph2 might be heterogeneous, although it is necessary to clarify whether this heterogeneous is “imprinted” or from the stimulation of milieu in “de novo” development. The gene discussed is IGHE; the disease is allergic disease.