Controlling B-cell Numbers, Activity Key to Preventing Inflammation in MS, Study Suggests

Jose Marques Lopes, PhD avatar

by Jose Marques Lopes, PhD |

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Appropriate control of immune B-cell numbers and activation in the nervous system is key to preventing inflammation in multiple sclerosis (MS), according to a study.

These findings also showed that patients with higher levels of a specific B-cell-regulating cell type had less disease activity.

The study, “Myeloid-derived suppressor cells control B cell accumulation in the central nervous system during autoimmunity,” was published in the journal Nature Immunology.

Fine-tuned regulation of a vast number of different cell types is required for proper immune system functioning. A particular cell type known as a myeloid-derived suppressor cell (MDSC) has been the subject of increasing research. MDSCs strongly suppress CD8+ T-cell responses against tumor cells, but less is known about their role in autoimmune diseases.

Besides T-cells, research also showed that MDSCs interact with immune B-cells, inhibiting their proliferation and differentiation. B-cells can develop into antibody-secreting cells, produce the pro-inflammatory molecule interleukin (IL)-6, and help T-cells carry their activity, all functions shown in preclinical studies of autoimmunity in the central nervous system (CNS).

Accumulation of B-cell aggregates in the CNS has been associated with the start and severity of the chronic disease phase in MS. However, the function of B-cells in this disease is not well-defined. Now, a team from Technical University of Munich has studied what controls the recruitment, maintenance, and function of B-cells in the cerebrospinal fluid (CSF) — the liquid surrounding the brain and spinal cord — and in CNS tissue.

“We were primarily interested in the control effect of the MDSCs on the B cells,” Thomas Korn, MD, PhD, the study’s senior author, said in a press release.

For this purpose, the scientists used the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. They found that removing MDSCs led to accumulation and activation of B-cells in the meninges — a three-layer structure that protects the nervous system — which was associated with production of IL-6 and GM-CSF, a molecule involved in the production and regulation of white blood cells.

When MDSCs were present in the CNS, they interacted with B-cells, controlling their number and lessening inflammation. The team also found that MDSCs are derived from neutrophils (a type of white blood cell) expressing the marker Ly6G+, which are recruited to the CNS during the disease course.

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“Thus [MDSCs] might selectively control the accumulation and cytokine secretion [namely of IL-6 and GM-CSF] of B cells in the inflamed CNS,” the scientists wrote.

When researchers tested the CSF of 25 patients (ages 18-60 years) with either relapsing-remitting MS or clinically isolated syndrome, they found that the greater the levels of B-cells containing the CD138+ marker, the lower the number of MDSCs. Importantly, MDSCs levels correlated with disease activity, as patients who had experienced a recent relapse or had ongoing disease activity had a lower number of these cells than those with no evidence of disease activity.

“There are already approved therapies in which B cells are regulated and suppressed on a medicinal basis,” Korn said. “Now we’ve provided an explanation of why this could be an effective treatment, at least in cases where the course of the disease is poor.”

Studies with larger numbers of MS patients are now in preparation.

In the future, the team aims to find the mechanisms driving B-cells’ effects in the nervous system. Korn suggested that direct B-cell-mediated recruitment of other immune cells, or the activation of immune cells in the blood and lymph systems followed by migration to the CNS are two possibilities.

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