Abstract
A fast antibody response can be critical to contain rapidly dividing pathogens. This can be achieved by the expansion of antigen-specific B cells in response to T-cell help followed by differentiation into plasmablasts. MicroRNA-155 (miR-155) is required for optimal T-cell-dependent extrafollicular responses via regulation of PU.1, although the cellular processes underlying this defect are largely unknown. Here, we show that miR-155 regulates the early expansion of B-blasts and later on the survival and proliferation of plasmablasts in a B-cell-intrinsic manner, by tracking antigen-specific B cells in vivo since the onset of antigen stimulation. In agreement, comparative analysis of the transcriptome of miR-155-sufficient and miR-155-deficient plasmablasts at the peak of the response showed that the main processes regulated by miR-155 were DNA metabolic process, DNA replication, and cell cycle. Thus, miR-155 controls the extent of the extrafollicular response by regulating the survival and proliferation of B-blasts, plasmablasts and, consequently, antibody production.
Highlights
Optimal humoral responses against foreign T-dependent antigens require crosstalk between B cells and CD4+ T cells
We previously showed that mice lacking miR-155 in B cells produce a lower number of IgM- and IgGsecreting plasmablasts relative to their wild-type counterparts (Vigorito et al, 2007)
We previously showed that miR-155 is critical to sustain an efficient extrafollicular response in a B-cell–intrinsic manner and that this can be attributed in part to miR-155 regulation of PU.1 (Lu et al, 2014)
Summary
Optimal humoral responses against foreign T-dependent antigens require crosstalk between B cells and CD4+ T cells. Gene expression analysis of miR-155–deficient plasmablasts revealed dysregulation of genes involved in proliferation, including DNA replication, cell cycle progression, and chromatin organisation.
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