IL21 and systemic lupus erythematosus: Since IL-10 and deficient co-stimulatory molecule expression appear to be a novel mechanism of self-tolerance employed by the pre-naïve B cells, a defect in pre-naïve B-cell functions could lead to a break in self-tolerance, especially in the SLE milieu, where expansion of the pre-naïve B cells has been found [3, 4], and the immune system is intensely activated as evidenced by elevated B cell-activating factor (BAFF) levels, hyperexpression of CD40L on T cells, and/or increased levels of certain cytokines such as IL-21 [50–53].