Autoimmune T cell - B cell interaction in experimental autoimmune encephalomyelitis

Although Multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) are known as T cell-mediated autoimmune diseases, there is increasing evidence that B cells also play a critical role in their pathogenesis. However, there are conflicting data about the exact role of B cells in the pathogenic process. To study the interaction of MOG-specific T and B cells in the course of actively induced EAE, we developed a model enabling us to track and analyze the cells ex vivo during disease progression. We induced EAE with the encephalitogenic MOGp35-55 peptide and found that the transfer of MOG-specific B cells had a disease promoting effect with an accelerated onset. When we focused on the underlying mechanism, we could show that MOG-specific B cells did not enhance MOG-specific T cell proliferation, activation or differentiation during the activation phase or immediately before EAE onset. Moreover, MOG-specific B cells did not enhance T cell activation in the reactivation phase within the CNS in our experimental model. The presence of MOG-specific B cells had no impact on the number of circulating inflammatory myeloid cells. Furthermore, endothelial cells of spinal cord microvessels displayed similar adhesion molecule and chemokine expression levels in the presence of MOG-specific B cells. The accelerated onset was accompanied by an increased number of CNS infiltrated T cells, leading to the speculation that MOG-specific B cells might influence T cell trafficking. The latter is supported by our finding that peripheral MOG-specific T cells showed an enhanced expression of CXCR4 and CCR6 in the presence of MOG-specific B cells. Our clinical data revealed that the presence of activated MOG-specific B cells is critically required for the accelerated disease onset, as activated MOG-unspecific B cells had no effect on the disease onset. When we focused on the mechanism utilized by MOG-specific B cells to promote disease initiation, we found that B cells with an impaired development into antibody secreting plasma cells did not accelerate the disease onset. This led to the conclusion that, even in EAE induced by MOG peptide, B cells promote the initiation of EAE by their secretion of MOG-specific antibodies