Belly-born B cells bathe the brain

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Science Immunology  01 Feb 2019:
Vol. 4, Issue 32, eaaw7721
DOI: 10.1126/sciimmunol.aaw7721


IgA-expressing antibody secreting cells that are formed in the gut travel to the brain to diminish inflammation during multiple sclerosis exacerbations.

There are a wide range of immune cell types that populate the brain tissue of patients with multiple sclerosis (MS). The infiltrate can include CD4+ T and CD8+ T cells, monocytes, natural killer cells and B cells, including the antibody-secreting cell (ASC) B cell subsets—plasma cells and plasmablasts. Among the ACSs in MS brains are those that express immunoglobulin A (IgA). These cells are most often found in the gut, where they interact with intestinal antigens, particularly microbiota, to mediate mutualism with the host. Consequently, it is rather unexpected for these IgA ASCs to be found in the MS brain. Their residence there, of course, raises questions regarding their contribution to neuroinflammation.

Rojas et al. have provided important answers concerning the ASCs’ role. Using a number of specialized B cell–tailored murine models of MS [experimental autoimmune encephalitis (EAE)], the team demonstrated that in EAE intestinal ASCs are decreased, and IgA ASCs are present in the central nervous system (CNS). Importantly, the authors provided evidence for a similar mechanism in humans. They showed that MS patients experiencing a disease relapse harbor reduced IgA–coated bacteria—a proxy of intestinal ASC presence—compared with patients in remission and non-MS control participants. Moreover, an adoptive transfer of intestinal ASC cells—most of which are IgA+—ameliorates EAE, and the transferred cells are detected in the CNS. The mechanism of this effect was further shown to depend not on the IgA per se but rather on intestinal IgA ASC interleukin-10 (IL-10) expression. In parallel experiments, the authors provided evidence that B cell activating factor (BAFF)–overexpressing mice—the consequence of which is a surplus of gut IgA ASCs—have increased baseline brain IgA and are resistant to EAE, again via an IL-10 mechanism.

In addition to providing support for an IL-10–dependent, protective role of IgA ASCs in CNS autoimmunity, these findings indirectly provide insight into MS treatment mechanisms that remain poorly understood. Specifically, anti-CD20 (rituximab)–mediated B cell depletion therapy, which is highly effective in treating MS, does not target ASCs, leaving them to deliver their anti-inflammatory effects to the CNS.

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