Glutamine promotes the generation of B10 + cells via the mTOR/GSK3 pathway

We studied the alloreactive properties of donor T cells obtained from F1 mice that had recovered from the allosuppression of acute graft-vs.-host disease (GVHD) and showed mild symptoms of chronic GVHD, i.e., so-called secondary chronic GVHD. To this end, we used (B10 x DBA/2)F1 mice that had been injected with 10(8) B10 spleen cells 100-150 d previously. Such GVHD F1 mice were repopulated by lympho-hematopoietic cells of donor (B10) origin, which exhibited split tolerance towards the host: Whereas F1-specific donor T helper (Th) cells as well as T cells proliferating in the mixed lymphocyte reaction were readily demonstrable, F1-specific T suppressor (Ts) and T killer (Tk) cells were not, or were hardly, detectable; responses against third-party alloantigens were normal. Upon adoptive transfer to nonirradiated secondary recipients, the B10 cells obtained from the repopulated GVH F1 mice induced F1-specific enlargement of the draining popliteal lymph node and enhancement of the IgG formation therein. B10 cells of the same kind were unable, however, to induce lethal GVHD upon transfer to 950 rad-irradiated secondary (B10 x DBA/2)F1 recipients. We conclude that alloactivated donor Ts/Tk cells disappear from the host at a relatively early stage of GVHD, i.e., at the end of acute GVHD , presumably because they are short-lived. By contrast, the longevity of alloactivated donor Th cells causes the symptoms of secondary chronic GVHD.

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Preconception allergen sensitization can induce B10 cells in offspring: a potential main role for maternal IgG

Allergy Asthma & Clinical Immunology ◽

10.1186/s13223-017-0195-8 ◽

2017 ◽

Vol 13 (1) ◽

Cited By ~ 9

Author(s):

Marília Garcia de Oliveira ◽

Luana de Mendonça Oliveira ◽

Aline Aparecida de Lima Lira ◽

Fábio da Ressureição Sgnotto ◽

Alberto José da Silva Duarte ◽

...

Keyword(s):

Main Role ◽

Allergen Sensitization ◽

B10 Cells ◽

Maternal Igg

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Altered frequency of CD24highCD38high transitional B cells in patients with cardiac involvement of chronic Chagas disease

10.1101/684589 ◽

2019 ◽

Author(s):

Magalí C. Girard ◽

Gonzalo R. Acevedo ◽

Micaela S. Ossowski ◽

Paula B. Alcaráz ◽

Marisa Fernández ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Chagas Disease ◽

Peripheral Blood ◽

Cardiac Involvement ◽

Mononuclear Cells ◽

Regulatory Function ◽

Chronic Patients ◽

B10 Cells ◽

Chronic Chagas Disease

ABSTRACTThe cardiomyopathy developed by patients with chronic Chagas disease (CCD), one of the most severe consequences of T. cruzi infection, is mainly associated with an imbalance between an excessive inflammatory reaction and a defective immunomodulatory profile cause by host-parasite interaction. Despite the growing importance of the regulatory function of B-cells in many malignancies, few studies have addressed their immunosuppressive role in chronic Chagas disease. In this work, we tackled this issue by studying the proportion of different B cell subpopulations and their capacity to secrete IL-10 in individuals with distinct clinical forms of CCD. Seven-colour flow cytometry was performed to examine the peripheral blood B cell compartment in chronic Chagas disease (CCD) patients with and without cardiac manifestations (n=10 for each group) and non-infected donors (n=9). Peripheral blood mononuclear cells (PBMC) were incubated for 5h with PMA, ionomicyn and brefeldin A. According to the expression of markers CD19, CD24 and CD38, we showed an expansion of total B cell and transitional CD24highCD38high B cell subsets in CCD patients with cardiac involvement compared to non-infected donors. Furthermore, although no differences were observed in the frequency of total IL-10 producing B cells (B10) among the groups, CCD patients with cardiac involvement showed a statistically significant increased proportion of naïve B10 cells and a tendency to an increased frequency of transitional B10 cells compared to non-infected donors. These findings suggest that immature transitional CD24highCD38high B cells are greatly expanded in patients with the cardiac form of chronic Chagas disease and these cells retain their ability to secrete IL-10 compared to non-infected donors. Furthermore, the distribution of naïve, transitional and memory B cells inside the B10 cells followed the same pattern in chronic patients without cardiac involvement and non-infected individuals. Our work provides insight into the phenotypic distribution of regulatory B cell in CCD, an important step towards new strategies to prevent cardiomiopathy associated with T. cruzi infection.

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The role of B regulatory (B10) cells in inflammatory disorders and their potential as therapeutic targets

International Immunopharmacology ◽

10.1016/j.intimp.2019.106111 ◽

2020 ◽

Vol 78 ◽

pp. 106111 ◽

Cited By ~ 1

Author(s):

Hongxia Wu ◽

Zhaoliang Su ◽

Prince Amoah Barnie

Keyword(s):

Therapeutic Targets ◽

Inflammatory Disorders ◽

B10 Cells

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The Potential of IgG to Induce Murine and Human Thymic Maturation of IL-10+ B Cells (B10) Revealed in a Pilot Study

Cells ◽

10.3390/cells9102239 ◽

2020 ◽

Vol 9 (10) ◽

pp. 2239

Author(s):

Amanda Harumi Sabô Inoue ◽

Aline Aparecida de Lima Lira ◽

Marília Garcia de-Oliveira ◽

Thamires Rodrigues de Sousa ◽

Fábio da Ressureição Sgnotto ◽

...

Keyword(s):

B Cells ◽

Mononuclear Cells ◽

Inflammatory Diseases ◽

Allergen Challenge ◽

Serum Samples ◽

Peripheral Blood Mononuclear ◽

Maturation Stages ◽

B10 Cells

Regulatory B (B10) cells can control several inflammatory diseases, including allergies; however, the origin of peripheral B10 cells is not fully understood, and the involvement of primary lymphoid organs (PLOs) as a primary site of maturation is not known. Here, using a murine model of allergy inhibition mediated by maternal immunization with ovalbumin (OVA), we aimed to evaluate whether B10 cells can mature in the thymus and whether IgG can mediate this process. Female mice were immunized with OVA, and offspring thymus, bone marrow, spleen, lung, and serum samples were evaluated at different times and after passive transfer of purified IgG or thymocytes. A translational approach was implemented using human nonatopic thymus samples, nonatopic peripheral blood mononuclear cells (PBMCs), and IgG from atopic or nonatopic individuals. Based on the expression of CD1d on B cells during maturation stages, we suggest that B10 cells can also mature in the murine thymus. Murine thymic B10 cells can be induced in vitro and in vivo by IgG and be detected in the spleen and lungs in response to an allergen challenge. Like IgG from atopic individuals, human IgG from nonatopic individuals can induce B10 cells in the infant thymus and adult PBMCs. Our observations suggest that B10 cells may mature in the thymus and that this mechanism may be mediated by IgG in both humans and mice. These observations may support the future development of IgG-based immunoregulatory therapeutic strategies.

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