Primary B cell repertoire remodeling to achieve humoral transplantation tolerance

Parsons, Ronald F.; Redfield, Robert; Rodríguez, Eduardo; Mustafa, Moiz M.; Vivek, Kumar; Murayama, Michael; Naji, Ali; Noorchashm, Hooman

doi:10.1016/j.smim.2011.08.016

Cited by 8 publications

(8 citation statements)

References 52 publications

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Section: Discussionmentioning

confidence: 99%

“…Many studies have shown that B-cell depletion ameliorates, prevents and in some instances can reverse autoimmunity [45], [89], [90], [91], [92], [93], [94], [95]. Mechanistic insights indicate anergy and immune deviation along with an increased threshold for antigen presentation as operationally-underlying the disease prevention and improvement [45], [89], [90], [91], [92], [93], [94], [95]. Accumulating data, however, strongly suggest that B-cell depletion is followed by a period of homeostatic expansion of B-1 type, transitional B-lymphocytes, and their progenitors [96], [97], [98], [99] and the surface phenotypes of those cells are strongly suggestive of B-cells with a regulatory, immunosuppressive ability [97], [98], although this has not been formally demonstrated.…”

Section: Discussionmentioning

confidence: 99%

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Involvement of Suppressive B-Lymphocytes in the Mechanism of Tolerogenic Dendritic Cell Reversal of Type 1 Diabetes in NOD Mice

Phillips

Engman

et al. 2014

PLoS ONE

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The objective of the study was to identify immune cell populations, in addition to Foxp3+ T-regulatory cells, that participate in the mechanisms of action of tolerogenic dendritic cells shown to prevent and reverse type 1 diabetes in the Non-Obese Diabetic (NOD) mouse strain. Co-culture experiments using tolerogenic dendritic cells and B-cells from NOD as well as transgenic interleukin-10 promoter-reporter mice along with transfer of tolerogenic dendritic cells and CD19+ B-cells into NOD and transgenic mice, showed that these dendritic cells increased the frequency and numbers of interleukin-10-expressing B-cells in vitro and in vivo. The expansion of these cells was a consequence of both the proliferation of pre-existing interleukin-10-expressing B-lymphocytes and the conversion of CD19+ B-lymphcytes into interleukin-10-expressing cells. The tolerogenic dendritic cells did not affect the suppressive activity of these B-cells. Furthermore, we discovered that the suppressive murine B-lymphocytes expressed receptors for retinoic acid which is produced by the tolerogenic dendritic cells. These data assist in identifying the nature of the B-cell population increased in response to the tolerogenic dendritic cells in a clinical trial and also validate very recent findings demonstrating a mechanistic link between human tolerogenic dendritic cells and immunosuppressive regulatory B-cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Involvement of Suppressive B-Lymphocytes in the Mechanism of Tolerogenic Dendritic Cell Reversal of Type 1 Diabetes in NOD Mice

Phillips

Engman

et al. 2014

PLoS ONE

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“…Adding RTX to rATG would be expected to further deplete the B-cell pool and allow for B-cell reconstitution in the presence of alloantigen and diminished T cell help. Thus, the current induction protocol may have led to a clinical circumstance allowing for remodeling of the B-cell repertoire towards a more toleragenic phenotype (Adams & Newell, 2012;Parsons et al, 2012;Tchao & Turka, 2012).…”

Section: Discussionmentioning

confidence: 99%

Combined Induction Therapy with Rabbit Antithymocyte Globulin and Rituximab in Highly Sensitized Renal Recipients

Laftavi

Pankewycz

Lin

et al. 2015

Immunological Investigations

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Compared to non-sensitized renal transplant recipients, patients with preformed alloantibodies are at greater risk of cellular and humoral rejection and premature graft failure. We explored the effects of adding B-cell depleting agent (rituximab) to standard rabbit anti-thymocyte globulin (rATG) induction regimen for patients with panel reactive antibody levels >50%. Following induction therapy, 14 recipients were given two doses of rituximab (375 mg/m(2)) within the first month post-transplantation. Their long-term outcomes were compared to a historical control group of 23 recipients who received rATG alone. Graft survival at 5 years was superior with combination therapy compared to induction therapy alone (92.9 versus 48.3%, respectively, p = 0.02). While 30% of the rATG alone group experienced cellular rejection and 26% humoral rejection, none of rituximab plus rATG renal transplant recipients group had rejection. Thus, addition of rituximab to rATG provided superior outcomes to rATG alone. This combination induction therapy should be considered for a high-risk population.

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“…43 The use of Tocilizumab and IVIG has been shown to reduce the number of antibodies in kidney transplant recipients and may be an effective therapy for sensitized heart transplant patients. 46 Beyond immunosuppressive therapies, the ability to perform ABO-incompatible heart transplantation in infants with precision provides an opportunity for methodical understanding of accommodation. 45 In vivo studies of BLyS have shown efficacy in deleting novel alloreactive antibodies at an early stage in B-cell lifespan.…”

Section: How S Hould Patients Underg O De S En S Itiz Ati On?mentioning

confidence: 99%

Desensitization in heart transplant recipients: Who, when, and how

Shah

Patel

2019

Clinical Transplantation

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The number of heart transplant candidates who have pre-formed antibodies against human leukocyte antigens (HLAs) is increasing over time. The purpose of this review is to discuss the process of antibody desensitization for heart transplant candidates. Specifically, we review the current status of antibody detection including identification, strength, and potential pathogenicity. We discuss which patients and when should they undergo desensitization therapies during heart transplant evaluation. Specific therapies including mechanical removal of antibodies, intravenous immunoglobulins, and novel immunosuppressive agents targeting antibody production will be discussed. Finally, future research strategies to develop novel desensitization therapies for heart transplant candidates will be reviewed. K E Y W O R D Sdesensitization, heart disease, sensitization

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Primary B cell repertoire remodeling to achieve humoral transplantation tolerance

Cited by 8 publications

References 52 publications

Involvement of Suppressive B-Lymphocytes in the Mechanism of Tolerogenic Dendritic Cell Reversal of Type 1 Diabetes in NOD Mice

Involvement of Suppressive B-Lymphocytes in the Mechanism of Tolerogenic Dendritic Cell Reversal of Type 1 Diabetes in NOD Mice

Combined Induction Therapy with Rabbit Antithymocyte Globulin and Rituximab in Highly Sensitized Renal Recipients

Desensitization in heart transplant recipients: Who, when, and how

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