B -cells Drive auto-T-cells to the Brain

Multiple sclerosis (MS) has long been a disease in which the cause is unclear. Researchers believe MS to be a T cell centered autoimmune disease, with little or no B cell involvement. In fact, previous suggestions that B cells had anything to do with the pathology of MS were mostly ignored. It wasn’t until the success of therapies depleting malignant B cells that the importance of B cell involvement was credited.

A recent study performed by Jenna Pappalardo and Kevin O'Connor the Yale University School of Medicine helps to reveal the details surrounding the role B cells play in their contribution to MS. Specifically the authors of the recent publication in Science Immunology study how B cells influence the T cells that populate MS of the brain.

Multiple sclerosis is an unpredictable, often disabling disease of the central nervous system that disrupts the flow of information within the brain, and between the brain and body. The cause of MS is still unknown, but it is predicted that the disease is triggered by an unidentified environmental factor in genetically predisposed individuals.

The mechanisms that are at play that allow for B cell contribution to MS are not defined. To this end, the co-authors investigated how B cells influence the T cells that populate the MS brain. It is a recognized fact that the MS-derived T cells will undergo increased auto-proliferation, the ability to spontaneously develop with no antigenic or exogenous stimulation.

The research team identified memory C cells as critical drivers of T cell auto-proliferation through human leukocyte antigen (HLA)-DR15 haplotype. The HLA-DR15 haplotype is a distinguishing genetic risk factor for those who develop MS. It was observed that T cell auto-proliferation decreased after B cell depleting therapies. After characterizing the auto-proliferating T cells, the work revealed that the cells are capable of brain-homing due to T helper cells expression of chemokine receptors that aid in brain entry.

The team of researchers performed T cell receptor sequencing to confirm auto-proliferating clones present in the periphery are enriches in brain lesions. This result is supportive of the B cell involvement of autoreactive and potential pathogenic T cell responses in MS.

The observations provided by this team have created a paradigm shift for understanding B cells in MS. Also, the results stimulate questions regarding B cells and auto-proliferating T cells such as the understanding of the elevation of auto-proliferative cells during remission and the specificity of the activating B cells.

Currently, those suffering from MS utilize a comprehensive approach that involves modification of the disease course, treatment of exacerbation, management of symptoms, promotion of function via rehabilitation, and emotional support.

Sources: Science-Immunology, NMSS