Title |
Human central nervous system astrocytes support survival and activation of B cells: implications for MS pathogenesis
|
---|---|
Published in |
Journal of Neuroinflammation, April 2018
|
DOI | 10.1186/s12974-018-1136-2 |
Pubmed ID | |
Authors |
Hanane Touil, Antonia Kobert, Nathalie Lebeurrier, Aja Rieger, Philippe Saikali, Caroline Lambert, Lama Fawaz, Craig S. Moore, Alexandre Prat, Jennifer Gommerman, Jack P. Antel, Yasuto Itoyama, Ichiro Nakashima, Amit Bar-Or, for the Canadian B Cell Team in MS |
Abstract |
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 allogeneic 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | 29% |
Canada | 1 | 14% |
Unknown | 4 | 57% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 4 | 57% |
Scientists | 2 | 29% |
Science communicators (journalists, bloggers, editors) | 1 | 14% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 92 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 14 | 15% |
Student > Ph. D. Student | 13 | 14% |
Student > Bachelor | 12 | 13% |
Student > Master | 9 | 10% |
Student > Postgraduate | 7 | 8% |
Other | 18 | 20% |
Unknown | 19 | 21% |
Readers by discipline | Count | As % |
---|---|---|
Neuroscience | 18 | 20% |
Medicine and Dentistry | 17 | 18% |
Immunology and Microbiology | 9 | 10% |
Agricultural and Biological Sciences | 8 | 9% |
Biochemistry, Genetics and Molecular Biology | 7 | 8% |
Other | 6 | 7% |
Unknown | 27 | 29% |