STAT-3 Activation by Differential Cytokines Is Critical for Human In Vivo–Generated Plasma Cell Survival and Ig Secretion
Year: 2013
Type: article
Abstract: Maturation and survival of plasma cells (PCs) depends on extrinsic factors provided in specialized niches. In addition, B lymphocyte differentiation into PCs requires the activation of the JAK-STAT-3 pathway. However, whether STAT-3 is needed only during the transition of B lymphocytes to PC, or it is also involved in the survival and function of PCs at different stages of maturation, has not been unequivocally clarified. This study analyzes the effect of IL-10, IL-21, and IL-6 on human in vivo-generated PCs isolated from secondary lymphoid organs, blood (circulating, recently Ag-induced PCs), and bone marrow. PCs from these different organs show specific profiles of receptors for, and responsiveness to, these cytokines required for their survival and sustained Ab secretion. However, IL-10, IL-21, and IL-6 commonly induce STAT-3 phosphorylation in the three PC subsets, and all of their effects are exerted strictly through the STAT-3 activation. The inhibition or nonactivation of this pathway in the three PC populations impairs not only the effect of STAT-3-activating cytokines, but also the action of other cytokines important at the PC level, including a proliferation-induced ligand, BAFF, insulin-like growth factor 1, vascular endothelial growth factor, and stromal cell-derived factor-1α. These results indicate that STAT-3 activation is critical for human PCs throughout their maturation.
Source: The Journal of Immunology
Institution: Hospital Universitario Puerta del Mar
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2148437680