Sunday, 22 April 2018

The B Team implicate star cells (Astrocytytes) as important B cell factors


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.

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. 

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

Saturday, 21 April 2018

Prof G the feminist

Three things happened to me this week that made realise that I am a feminist.


Friday, 20 April 2018

Is the B cell idea broken?....Sort of Th17 and Th1 are the problem.

The B cell hypothesis gains momentum with the Pharma Industry, but do our academic colleagues know better and it really is the TH17 cell at the top of the pyramid.

Thursday, 19 April 2018

Vaccines and Vaccinations: The Big Differentiator

I predict vaccines and the timing of vaccinations will in time become a major differentiator between the maintenance therapies and the immune reconstitution therapies (IRTs). 



What do you think? 

Wednesday, 18 April 2018

Guest post: Your attention please: MS hurts!



Visual impairment, sensory disturbances, weakness and fatigue are among the most commons symptoms in MS, but there are others such as pain, which is highly distressing and can easily affect day-to-day life. This symptom is often difficult to describe by patients and is sometimes difficult to diagnose and treat by clinicians.

Tuesday, 17 April 2018

EBV and the not so magnificant 7. A cause of autoimmunity

New genetic research has linked EBV infection to seven autoimmune diseases and include multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, juvenile idiopathic arthritis, celiac disease and SLE

What do they have in common?


A glass half full? Benign MS in Australia

Are you a glass-half-full or a glass-half-empty person? 


Monday, 16 April 2018

Reflections on all things MS from Stornoway

We have just finished our 2018 Barts-MS Research Day on Stornoway with the Glasgow-MS team. The experience has been very humbling and quite and an eye-opener in terms of living with a chronic disease, such as MS, on a remote Island.

Barts-MS and Glasgow-MS hugging the Callanish Stones, Western Isles.


Saturday, 14 April 2018