Figure 2. Hypothetical mechanistic scheme for the modulation of IgE production by heavy metals. There are mainly two pathways that are involved in the production of IgE; these include a Th2-derived IL-4 dependent pathway and T follicular helper (Tfh) cell-dependent, IL-4-independent pathway. Our results and previous work indicate that Pb or Hg exposures can induce several types of IgE. Additionally, these exposures can reportedly stimulate IL-4 production, thus suggesting that heavy metal-dependent increases in IL-4 levels might be one of the causes of IgE production. Also, Hg exposures are known to alter the phosphorylation status of Syk (spleen tyrosine kinase), which mediates B cell differentiation. This could be an alternative for the induction of IgE production, especially by Hg.