Induction of CD4+ T-cell anergy and apoptosis by activated human B cells

Tretter, Theresa; Venigalla, Ram Kumar; Eckstein, Volker; Saffrich, Rainer; Sertel, Serkan; Ho, Anthony D.; Lorenz, Hanns‐Martin

doi:10.1182/blood-2008-02-140087

Cited by 69 publications

(73 citation statements)

References 55 publications

(65 reference statements)

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“…We did not find any involvement of the Fas-FasL pathway in this process (data not shown), but alternative pathways have been described as inducing apoptosis, and GzmB is one of them. 56 These data suggest a pivotal role for GzmB in regulation by B cells in our patients through cell death induction and T cell proliferation inhibition, a mechanism already described for Tregs after polyclonal and antigen-specific activation. 54 Interestingly, we found that B cells had no effect on TNF-a and IFN-g production.…”

Section: Discussionsupporting

confidence: 72%

Tolerant Kidney Transplant Patients Produce B Cells with Regulatory Properties

Chesneau¹,

Michel²,

Dugast³

et al. 2015

Journal of the American Society of Nephrology

138

125

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Whereas a B cell-transcriptional profile has been recorded for operationally tolerant kidney graft patients, the role that B cells have in this tolerance has not been reported. In this study, we analyzed the role of B cells from operationally tolerant patients, healthy volunteers, and kidney transplant recipients with stable graft function on T cell suppression. Proliferation, apoptosis, and type I proinflammatory cytokine production by effector CD4 + CD25 2 T cells were measured after anti-CD3/anti-CD28 stimulation with or without autologous B cells. We report that B cells inhibit CD4 + CD25 2 effector T cell response in a dosedependent manner. This effect required B cells to interact with T-cell targets and was achieved through a granzyme B (GzmB)-dependent pathway. Tolerant recipients harbored a higher number of B cells expressing GzmB and displaying a plasma cell phenotype. Finally, GzmB + B-cell number was dependent on IL-21 production, and B cells from tolerant recipients but not from other patients positively regulated both the number of IL-21 + T cells and IL-21 production, suggesting a feedback loop in tolerant recipients that increases excessive B cell activation and allows regulation to take place. These data provide insights into the characterization of B cell-mediated immunoregulation in clinical tolerance and show a potential regulatory effect of B cells on effector T cells in blood from patients with operationally tolerant kidney grafts.

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Section: Discussionsupporting

confidence: 72%

Tolerant Kidney Transplant Patients Produce B Cells with Regulatory Properties

Chesneau¹,

Michel²,

Dugast³

et al. 2015

Journal of the American Society of Nephrology

138

125

View full text Add to dashboard Cite

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“…One of these molecules is CD25, which is also expressed on Treg (37,38). A recent study showed the development of large, CD25 þ B cells with regulatory potential after polyclonal activation with different TLR-agonistic stimuli (43). Part of the regulatory effect identified in CD25-expressing B cells may therefore be due to IL-2 deprivation (37,38 Although the existence of tumor-infiltrating B cells has been previously described (27,45), their significance for solid tumors remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Interleukin 21–Induced Granzyme B–Expressing B Cells Infiltrate Tumors and Regulate T Cells

et al. 2013

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The pathogenic impact of tumor-infiltrating B cells is unresolved at present, however, some studies suggest that they may have immune regulatory potential. Here, we report that the microenvironment of various solid tumors includes B cells that express granzyme B (GrB, GZMB), where these B cells can be found adjacent to interleukin (IL)-21-secreting regulatory T cells (Treg) that contribute to immune tolerance of tumor antigens. Because Tregs and plasmacytoid dendritic cells are known to modulate T-effector cells by a GrB-dependent mechanism, we hypothesized that a similar process may operate to modulate regulatory B cells (Breg). IL-21 induced outgrowth of B cells expressing high levels of GrB, which thereby limited T-cell proliferation by a GrB-dependent degradation of the T-cell receptor z-chain. Mechanistic investigations into how IL-21 induced GrB expression in B cells to confer Breg function revealed a CD19

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“…This finding is in clear contrast with the IL-10-driven regulatory mechanisms often ascribed to Bregs (10). However, it has been reported that mature Bregs can also use regulatory pathways that do not depend on IL-10, such as cell-to-cell interactions involving MHC (47) or B7 molecules (48) and blockade of Teff expansion via FasL-induced apoptosis (49)(50)(51). Evidently, the inflammatory signals and cytokines they encounter in their microenvironment engender diverse immunosuppressive mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Innate pro–B-cell progenitors protect against type 1 diabetes by regulating autoimmune effector T cells

Montandon

Korniotis

Layseca-Espinosa

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Significance Immunoregulatory poperties have been principally ascribed to various mature immune cell types, including regulatory B cells. An immature B-cell progenitor population endowed with suppressive properties per se or after differentiation into more mature regulatory B cells has not been demonstrated as yet. We now describe a pro–B-cell progenitor population that emerged upon stimulation with the Toll-like receptor-9 ligand CpG and prevented disease upon adoptive transfer into autoimmune type 1 diabetes-prone mice. Effector T cells were the target of immunoregulatory pro-B cells and of their mature progeny. Such protective pro-B cells could be instrumental for cell therapy of autoimmune diseases.

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Induction of CD4+ T-cell anergy and apoptosis by activated human B cells

Cited by 69 publications

References 55 publications

Tolerant Kidney Transplant Patients Produce B Cells with Regulatory Properties

Tolerant Kidney Transplant Patients Produce B Cells with Regulatory Properties

Interleukin 21–Induced Granzyme B–Expressing B Cells Infiltrate Tumors and Regulate T Cells

Innate pro–B-cell progenitors protect against type 1 diabetes by regulating autoimmune effector T cells

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