Innate lymphoid cells integrate stromal and immunological signals to enhance antibody production by splenic marginal zone B cells.
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ABSTRACT:
SUBMITTER: Magri G
PROVIDER: S-EPMC4005806 | BioStudies | 2014-01-01
REPOSITORIES: biostudies
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Project description:Splenic Marginal Zone B cells mount innate-like T cell-independent (TI) antibody responses to blood-borne antigens upon receiving activation signals from TACI-engaging factors BAFF and APRIL. The transcriptome analysis of splenic Marginal Zone (MZ) B cells was performed to verify which transcriptional programs are enhanced in the innate-like MZ B cell subset and to study the involvement of mTOR in MZ B cells activated via TACI. Overall design: Unstimulated human Marginal Zone and Follicular/Naive B cells were FACSorted from spleens of seven (MZ) and three (FO) adult healthy subjects for RNA isolation and Agilent analysis. Moreover, APRIL (500ng/ml) and Rapamycin (10nM) were used to dissect the involvement of mTOR in the induction of Class Switch Recombination and antibody production in MZ B cells activated through TACI.
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Project description:Macrophages are professional phagocytic cells that orchestrate innate immune responses and have considerable phenotypic diversity at different anatomical locations. However, the mechanisms that control the heterogeneity of tissue macrophages are not well characterized. Here we found that the nuclear receptor LXR? was essential for the differentiation of macrophages in the marginal zone (MZ) of the spleen. LXR-deficient mice were defective in the generation of MZ and metallophilic macrophages, which resulted in abnormal responses to blood-borne antigens. Myeloid-specific expression of LXR? or adoptive transfer of wild-type monocytes restored the MZ microenvironment in LXR?-deficient mice. Our results demonstrate that signaling via LXR? in myeloid cells is crucial for the generation of splenic MZ macrophages and identify an unprecedented role for a nuclear receptor in the generation of specialized macrophage subsets.
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