Figure 7.

Memory T cells against αB-crystallin cause derailment of the process. When sufficient numbers of αB-crystallin-reactive T cells encounter B cells within the CNS that present their target antigen at a sufficiently high concentration, things will go wrong. B cells lack CD14 and, therefore, fail to mount the regulatory and immune-suppressive response to αB-crystallin as seen in microglia and macrophages. Instead, they will allow the development of a substantial IFN-γ response by T cells (see Fig. 2C). This response changes everything since IFN-γ reprograms TLR signaling pathways in microglia and macrophages. Their originally protective response to αB-crystallin now changes into a full-blown destructive response, leading to tissue damage. Furthermore, it will cause substantial destabilization of the BBB and active recruitment of leucocytes, adding more fuel to the fire (Figure created with Biorender).