Extrinsic defect in B cells differentiation through alteration of T FH cells
Exploring T FH subsets involvement in Multiple Sclerosis course
We show that RRMS patients in relapse have a decreased frequency of ICOS + T FH cells compared to HC, a seducing hypothesis would be that during MS relapses a B cell reactivation occurs in periphery with the recruitment of ICOS + T FH cells in the germinal centers, explaining the relative decrease of circulating ICOS + T FH cells.
Interestingly, we found that activated PD 1 + T FH cells infiltrate the CSF of MS patients with a T FH 1 polarization.
We also show in this study an intrinsic defect in B cells differentiation in MS patients, and our results probably indicate an extrinsic defect in B cells differentiation through alteration of T FH cells function . Therefore, to assess the abilities of T FH cells to drive B cell differentiation, we developed a model of co-culture of B cells and autologous T FH cells.
To better characterize CSF - infiltrating T FH cells, we plan to perform RNA sequencing of these cells in the blood and the CSF
of MS patients.
Addressing these different questions on distinct groups of MS patients should help in the understanding of biological processes underlying these different forms of the same disease.