| 1. |
- Rosado, M. M., et al.
(författare)
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Spleen development is modulated by neonatal gut microbiota
- 2018
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Ingår i: Immunology Letters. - : Elsevier BV. - 0165-2478. ; 199, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- The full development of the mammalian immune system occurs after birth upon exposure to non self-antigens. The gut is the first site of bacterial colonization where it is crucial to create the appropriate microenvironment able to balance effector or tolerogenic responses to external stimuli. It is a well-established fact that at mucosal sites bacteria play a key role in developing the immune system but we ignore how colonising bacteria impact the maturation of the spleen. Here we addressed this issue. Taking advantage of the fact that milk SIgA regulates bacterial colonization of the newborn intestine, we generated immunocompetent mice born either from IgA pro-efficient or IgA deficient females. Having demonstrated that SIgA in maternal milk modulates neonatal gut microbiota by promoting an increased diversity of the colonizing species we also found that immunocompetent pups, not exposed to milk SIgA, fail to properly develop the FDC network and primary follicles in the spleen compromising the response to T-dependent antigens. The presence of a less diverse microbiota with a higher representation of pathogenic species leads to a fast replenishment of the marginal zone and the IgM plasma cell compartment of the spleen as well as IgA plasma cells in the gut. © 2018 European Federation of Immunological Societies
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| 2. |
- Farroni, C., et al.
(författare)
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Dysregulated miR-155 and miR-125b are related to impaired B-cell responses in down syndrome
- 2018
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Children with Down Syndrome (DS) suffer from immune deficiency with a severe reduction in switched memory B cells (MBCs) and poor response to vaccination. Chromosome 21 (HSA21) encodes two microRNAs (miRs), miR-125b, and miR-155, that regulate B-cell responses. We studied B- and T- cell subpopulations in tonsils of DS and age-matched healthy donors (HD) and found that the germinal center (GC) reaction was impaired in DS. GC size, numbers of GC B cells and Follicular Helper T cells (TFH) expressing BCL6 cells were severely reduced. The expression of miR-155 and miR-125b was increased in tonsillar memory B cells and miR-125b was also higher than expected in plasma cells (PCs). Activation-induced cytidine deaminase (AID) protein, a miR-155 target, was significantly reduced in MBCs of DS patients. Increased expression of miR-155 was also observed in vitro. MiR-155 was significantly overexpressed in PBMCs activated with CpG, whereas miR-125b was constitutively higher than normal. The increase of miR-155 and its functional consequences were blocked by antagomiRs in vitro. Our data show that the expression of HSA21-encoded miR-155 and miR-125b is altered in B cells of DS individuals both in vivo and in vitro. Because of HSA21-encoded miRs may play a role also in DS-associated dementia and leukemia, our study suggests that antagomiRs may represent pharmacological tools useful for the treatment of DS. © 2007 - 2018 Frontiers Media S.A. All Rights Reserved.
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| 3. |
- Marasco, E., et al.
(författare)
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B-cell activation with CD40L or CpG measures the function of B-cell subsets and identifies specific defects in immunodeficient patients
- 2017
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Ingår i: Eur J Immunol. - : Wiley. - 0014-2980. ; 47:1, s. 131-143
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Tidskriftsartikel (refereegranskat)abstract
- Around 65% of primary immunodeficiencies are antibody deficiencies. Functional tests are useful tools to study B-cell functions in vitro. However, no accepted guidelines for performing and evaluating functional tests have been issued yet. Here, we report our experience on the study of B-cell functions in infancy and throughout childhood. We show that T-independent stimulation with CpG measures proliferation and differentiation potential of memory B cells. Switched memory B cells respond better than IgM memory B cells. On the other hand, CD40L, a T-dependent stimulus, does not induce plasma cell differentiation, but causes proliferation of naive and memory B cells. During childhood, the production of plasmablasts in response to CpG increases with age mirroring the development of memory B cells. The response to CD40L does not change with age. In patients with selective IgA deficiency (SIgAD), we observed that switched memory B cells are reduced due to the absence of IgA memory B cells. In agreement, IgA plasma cells are not generated in response to CpG. Unexpectedly, B cells from SIgAD patients show a reduced proliferative response to CD40L. Our results demonstrate that functional tests are an important tool to assess the functions of the humoral immune system.
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