| 1. |
- Grimsholm, O., et al.
(författare)
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The Interplay between CD27(dull) and CD27(brig)(ht) B Cells Ensures the Flexibility, Stability, and Resilience of Human B Cell Memory
- 2020
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 30:9, s. 2963-
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Tidskriftsartikel (refereegranskat)abstract
- Memory B cells (MBCs) epitomize the adaptation of the immune system to the environment. We identify two MBC subsets in peripheral blood, CD27(dull) and CD27(bright) MBCs, whose frequency changes with age. Heavy chain variable region (VH) usage, somatic mutation frequency replacement-to-silent ratio, and CDR3 property changes, reflecting consecutive selection of highly antigen-specific, low cross-reactive antibody variants, all demonstrate that CD27(du)(ll) and CD27(bright) MBCs represent sequential MBC developmental stages, and stringent antigen-driven pressure selects CD27(du)(ll) into the CD27(bright) MBC pool. Dynamics of human MBCs are exploited in pregnancy, when 50% of maternal MBCs are lost and CD27(du)(ll) MBCs transit to the more differentiated CD27 bright stage. In the postpartum period, the maternal MBC pool is replenished by the expansion of persistent CD27(du)(ll) clones. Thus, the stability and flexibility of human B cell memory is ensured by CD27(du)(ll) MBCs that expand and differentiate in response to change.
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| 2. |
- Rosado, M. M., et al.
(författare)
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Purification and characterization of murine MZ and T2-MZP cells
- 2021
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Ingår i: Regulatory B Cells. Methods in Molecular Biology, vol 2270. Mion F., Tonon S. (eds). - New York, NY : Springer. - 1064-3745. - 9781071612361 ; , s. 3-25
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The spleen is the second major reservoir of B cells in the adult. In the spleen, cells, generated in the bone marrow, are selected, mature, and become part of the peripheral B-cell pool. Murine spleen comprises several B-cell subsets representing various maturation stages and/or cell functions. The spleen is a complex lymphoid organ organized into two main structures with different functions: the red and white pulp. The red pulp is flowed with blood while the white pulp is organized in primary follicles, with a B-cell area composed of follicular B cells and a T-cell area surrounding a periarterial lymphatic sheath. The frontier between the red and white pulp is defined as the marginal zone (MZ) and contains the MZ B cells. Because B cells, localized in different areas, are characterized by distinct expression levels of B-cell receptor (BCR) and of other surface markers, splenic B-cell subsets can be easily identified and purified by flow cytometry analyses and fluorescence-activated cell sorting (FACS). Here, we will focus on MZ B cells and on their precursors, giving some experimental hints to identify, generate, and isolate these cells. We will combine the use of FACS analysis and confocal microscopy to visualize MZ B cells in cell suspensions and in tissue sections, respectively. We will also give some clues to analyze B-cell repertoire on isolated MZ-B cells. © Springer Science+Business Media, LLC, part of Springer Nature 2021.
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| 3. |
- 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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| 4. |
- 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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| 5. |
- 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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| 6. |
- Friman, Vanda, 1952, et al.
(författare)
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Defective peripheral B cell selection in common variable immune deficiency patients with autoimmune manifestations
- 2023
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Ingår i: Cell Reports. - : Elsevier. - 2211-1247. ; 42:5
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Tidskriftsartikel (refereegranskat)abstract
- Common variable immune deficiency (CVID) is a heterogeneous disorder characterized by recurrent infections, low levels of serum immunoglobulins, and impaired vaccine responses. Autoimmune manifestations are common, but B cell central and peripheral selection mechanisms in CVID are incompletely understood. Here, we find that receptor editing, a measure of central tolerance, is increased in transitional B cells from CVID patients and that these cells have a higher immunoglobulin κ:λ ratio in CVID patients with autoimmune manifestations than in those with infection only. Contrariwise, the selection pressure in the germinal center on CD27bright memory B cells is decreased in CVID patients with autoimmune manifestations. Finally, functionally, T cell-dependent activation showed that naive B cells in CVID patients are badly equipped for activation and induction of mismatch repair genes. We conclude that central tolerance is functional whereas peripheral selection is defective in CVID patients with autoimmune manifestations, which could underpin the development of autoimmunity.
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