TLR7, IFNγ, and T-bet: Their roles in the development of ABCs in female-biased autoimmunity

• TLR7, IFNγ and BCR synergistically induce expression of T-bet in B cells.
• T-bet expressing B cells acquire distinct phenotype and become ABCs.
• Accumulation of ABCs in females may lead to a predisposition for the autoimmunity.
• TLR7 and IFNγ may drive gender-related differences in (auto)immune response.

The majority of autoimmune diseases have a strong gender bias, affecting mostly females. Gender-specific factors like sex-hormones, the presence or absence of a second X chromosome, and gender-specific gut microbiota may contribute to this bias. In this review we will discuss the role of the X chromosome encoded toll-like receptor 7 (TLR7) and interferon gamma (IFNγ) in the development of autoimmunity. We will also review recent data indicating how these factors may affect an immune response in a gender-dependent manner.