Human IL‐6‐Producing B Cells Promote the Differentiation of Monocytes Toward an Anti‐Inflammatory CD16⁺CD163⁺CD206⁺PD‐L1⁺ Phenotype in Tuberculosis

ABSTRACT The polarization of the monocyte/macrophage compartment toward an anti‐inflammatory profile is considered detrimental in tuberculosis (TB), but the factors controlling M2 polarization in this context are still poorly understood. Here, we found that B cells promote the differentiation of human monocytes toward an M2‐like activation program through a process primarily dependent on IL‐6 and the activation of STAT3 signaling in monocytes. This confers monocytes with immunomodulatory properties characterized by a reduced ability to produce proinflammatory cytokines and to stimulate IFNγ secretion by allogeneic T cells. Our findings were validated using B cells from TB patients, which constitutively produce high levels of IL‐6, underscoring the clinical relevance of our experimental observations. Collectively, our results indicate that human B‐cell‐derived IL‐6 might impair TB immunity by driving monocyte polarization toward an anti‐inflammatory phenotype.