The B Team inmplicates astrocytes
B cells accumulate in the CNS during MS. What keeps them going? In this study they find the astrocyte secrtetes factors that promote B cell survival.
Take a B cell out of its environment for a few days and you have a dead B cell. In contrast T cells last for much longer.
The Canadians have got their act together and have assembled a team to examine B cell activity. They show that astrocytes secrete factors that promote B cell survival.
Human central nervous system astrocytes support survival and activation of B cells: implications for MS pathogenesis.
Touil H, Kobert A, Lebeurrier N, Rieger A, Saikali P, Lambert C, Fawaz L, Moore CS, Prat A, Gommerman J, Antel JP, Itoyama Y, Nakashima I, Bar-Or A; Canadian B Cell Team in MS.
J Neuroinflammation. 2018 Apr 19;15(1):114.
The success of clinical trials of selective B cell depletion in patients with relapsing multiple sclerosis (MS) indicates B cells are important contributors to peripheral immune responses involved in the development of new relapses. Such B cell contribution to peripheral inflammation likely involves antibody-independent mechanisms. Of growing interest is the potential that B cells, within the MS central nervous system (CNS), may also contribute to the propagation of CNS-compartmentalized inflammation in progressive (non-relapsing) disease. B cells are known to persist in the inflamed MS CNS and are more recently described as concentrated in meningeal immune-cell aggregates, adjacent to the subpial cortical injury which has been associated with progressive disease. How B cells are fostered within the MS CNS and how they may contribute locally to the propagation of CNS-compartmentalized inflammation remain to be elucidated.
We considered whether activated human astrocytes might contribute to B cell survival and function through soluble factors. B cells from healthy controls (HC) and untreated MS patients were exposed to primary human astrocytes that were either maintained under basal culture conditions (non-activated) or pre-activated with standard inflammatory signals. B cell exposure to astrocytes included direct co-culture, co-culture in transwells, or exposure to astrocyte-conditioned medium. Following the different exposures, B cell survival and expression of T cell co-stimulatory molecules were assessed by flow cytometry, as was the ability of differentially exposed B cells to induce activation of T cells.
Secreted factors from both non-activated and activated human astrocytes robustly supported human B cell survival. Soluble products of pre-activated astrocytes also induced B cell upregulation of antigen-presenting cell machinery, and these B cells, in turn, were more efficient activators of T cells. Astrocyte-soluble factors could support survival and activation of B cell subsets implicated in MS, including memory B cells from patients with both relapsing and progressive forms of disease.
Our findings point to a potential mechanism whereby activated astrocytes in the inflamed MS CNS not only promote a B cell fostering environment, but also actively support the ability of B cells to contribute to the propagation of CNS-compartmentalized inflammation, now thought to play key roles in progressive disease.
The question is what are the factors that promote this B cell activity? This study didn’t report on their identity however,
They produce IL-6, Finally, astrocytes produce BAFF (B cell activating factor of the TNF family) and promote proliferation of B cells via cell-to-cell contact based on other studies.