Differential responses to R848 and IgG/IgM in EBV-transformed B cells from individuals with Down syndrome compared to disomic individuals.

Abstract

Abstract Down syndrome (Trisomy 21; T21) results from an extra copy of chromosome 21 and causes a myriad of abnormalities, including immune dysfunction. Recent studies of PBMCs in those with T21 have shown reduced numbers of naive B cells, and increases in differentiated B cells, perhaps contributing to increased autoreactive and inflammatory conditions. The receptor for IFNα is located on chromosome 21, and has been shown to be expressed and functional on cells with T21. IFNα has been suggested to play a role in B cell responses, but little is known about the role of IFNα and B cell interaction in those with T21. Herein, we sought to further evaluate B cells from individuals with T21 following in vitrostimulation, with the hypothesis that cells with T21 would have greater B cell activation and cytokine production due to the extra IFNα receptor, compared to their disomic counterparts. EBV-transformed B cells from individuals with and without T21 were cultured and stimulated with R848/IL2, IgG/IgM cocktail or media as a control. In our unstimulated controls our results were in alignment with previous studies that suggest B cells from those with T21 are more terminally differentiated; we also observed significantly increased expression of the activation marker CD86 on these cells compared to disomic individuals. However, when stimulated with either R848 or IgG/IgM we did not observe a significant difference in the ability of B cells to express activation marker CD86. No significant differences were observed among cytokine production. Thus, the extra IFNα receptor may not help in B cell responses to infections and instead drive B cells into a more consistent inflammatory state.