You are currently viewing the abstract.
View Full TextLog in to view the full text
AAAS login provides access to Science for AAAS members, and access to other journals in the Science family to users who have purchased individual subscriptions.
Register for free to read this article
As a service to the community, this article is available for free. Existing users log in.
More options
Download and print this article for your personal scholarly, research, and educational use.
Buy a single issue of Science for just $15 USD.
Eclipsing multiple sclerosis
B cell depletion therapy (BCDT) has been shown to limit inflammation in some cases of multiple sclerosis (MS); however, how exactly BCDT works has remained unclear. Now, Li et al. report that a subset of B cells that produce the cytokine granulocyte macrophage–colony stimulating factor (GM-CSF) contributes to MS pathogenesis. These cells are more frequent in MS patients than in healthy controls and increase proinflammatory myeloid responses. Moreover, production of these cells counterbalances the generation of interleukin-10 (IL-10)–producing regulatory B cells, which are thought to be protective in disease. After BCDT, the ratio of GM-CSF/IL-10–producing B cells is normalized, suggesting that BCDT may work in part by decreasing the number of pathogenic GM-CSF–producing B cells.
Abstract
B cells are not limited to producing protective antibodies; they also perform additional functions relevant to both health and disease. However, the relative contribution of functionally distinct B cell subsets in human disease, the signals that regulate the balance between such subsets, and which of these subsets underlie the benefits of B cell depletion therapy (BCDT) are only partially elucidated. We describe a proinflammatory, granulocyte macrophage–colony stimulating factor (GM-CSF)–expressing human memory B cell subset that is increased in frequency and more readily induced in multiple sclerosis (MS) patients compared to healthy controls. In vitro, GM-CSF–expressing B cells efficiently activated myeloid cells in a GM-CSF–dependent manner, and in vivo, BCDT resulted in a GM-CSF–dependent decrease in proinflammatory myeloid responses of MS patients. A signal transducer and activator of transcription 5 (STAT5)– and STAT6-dependent mechanism was required for B cell GM-CSF production and reciprocally regulated the generation of regulatory IL-10–expressing B cells. STAT5/6 signaling was enhanced in B cells of untreated MS patients compared with healthy controls, and B cells reemerging in patients after BCDT normalized their STAT5/6 signaling as well as their GM-CSF/IL-10 cytokine secretion ratios. The diminished proinflammatory myeloid cell responses observed after BCDT persisted even as new B cells reconstituted. These data implicate a proinflammatory B cell/myeloid cell axis in disease and underscore the rationale for selective targeting of distinct B cell populations in MS and other human autoimmune diseases.
- Copyright © 2015, American Association for the Advancement of Science
