B Quiet: Autoantigen-Specific Strategies to Silence Raucous B Lymphocytes and Halt Cross-Talk with T Cells in Type 1 Diabetes
Islet autoantibodies are the primary biomarkers used to predict type 1 diabetes (T1D) disease risk. They signal immune tolerance breach by islet autoantigen-specific B lymphocytes. T-B lymphocyte interactions that lead to expansion of pathogenic T cells underlie T1D development. Promising strategies...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/1/42 |
| _version_ | 1827698362773667840 |
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| author | Jamie L. Felton Holly Conway Rachel H. Bonami |
| author_facet | Jamie L. Felton Holly Conway Rachel H. Bonami |
| author_sort | Jamie L. Felton |
| collection | DOAJ |
| description | Islet autoantibodies are the primary biomarkers used to predict type 1 diabetes (T1D) disease risk. They signal immune tolerance breach by islet autoantigen-specific B lymphocytes. T-B lymphocyte interactions that lead to expansion of pathogenic T cells underlie T1D development. Promising strategies to broadly prevent this T-B crosstalk include T cell elimination (anti-CD3, teplizumab), B cell elimination (anti-CD20, rituximab), and disruption of T cell costimulation/activation (CTLA-4/Fc fusion, abatacept). However, global disruption or depletion of immune cell subsets is associated with significant risk, particularly in children. Therefore, antigen-specific therapy is an area of active investigation for T1D prevention. We provide an overview of strategies to eliminate antigen-specific B lymphocytes as a means to limit pathogenic T cell expansion to prevent beta cell attack in T1D. Such approaches could be used to prevent T1D in at-risk individuals. Patients with established T1D would also benefit from such targeted therapies if endogenous beta cell function can be recovered or islet transplant becomes clinically feasible for T1D treatment. |
| first_indexed | 2024-03-10T13:28:20Z |
| format | Article |
| id | doaj.art-b9f8cc58e5dc4879bfc2f33d64e8f1cd |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T13:28:20Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-b9f8cc58e5dc4879bfc2f33d64e8f1cd2023-11-21T08:41:20ZengMDPI AGBiomedicines2227-90592021-01-01914210.3390/biomedicines9010042B Quiet: Autoantigen-Specific Strategies to Silence Raucous B Lymphocytes and Halt Cross-Talk with T Cells in Type 1 DiabetesJamie L. Felton0Holly Conway1Rachel H. Bonami2Department of Pediatrics, Division of Pediatric Endocrinology and the Herman B. Wells Center for Pediatric Research, Indianapolis, IN 46202, USADepartment of Pediatrics, Division of Pediatric Endocrinology and the Herman B. Wells Center for Pediatric Research, Indianapolis, IN 46202, USADepartment of Medicine, Division of Rheumatology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USAIslet autoantibodies are the primary biomarkers used to predict type 1 diabetes (T1D) disease risk. They signal immune tolerance breach by islet autoantigen-specific B lymphocytes. T-B lymphocyte interactions that lead to expansion of pathogenic T cells underlie T1D development. Promising strategies to broadly prevent this T-B crosstalk include T cell elimination (anti-CD3, teplizumab), B cell elimination (anti-CD20, rituximab), and disruption of T cell costimulation/activation (CTLA-4/Fc fusion, abatacept). However, global disruption or depletion of immune cell subsets is associated with significant risk, particularly in children. Therefore, antigen-specific therapy is an area of active investigation for T1D prevention. We provide an overview of strategies to eliminate antigen-specific B lymphocytes as a means to limit pathogenic T cell expansion to prevent beta cell attack in T1D. Such approaches could be used to prevent T1D in at-risk individuals. Patients with established T1D would also benefit from such targeted therapies if endogenous beta cell function can be recovered or islet transplant becomes clinically feasible for T1D treatment.https://www.mdpi.com/2227-9059/9/1/42antibodiesautoantigenautoimmunityB cellsinsulinlymphocytes |
| spellingShingle | Jamie L. Felton Holly Conway Rachel H. Bonami B Quiet: Autoantigen-Specific Strategies to Silence Raucous B Lymphocytes and Halt Cross-Talk with T Cells in Type 1 Diabetes Biomedicines antibodies autoantigen autoimmunity B cells insulin lymphocytes |
| title | B Quiet: Autoantigen-Specific Strategies to Silence Raucous B Lymphocytes and Halt Cross-Talk with T Cells in Type 1 Diabetes |
| title_full | B Quiet: Autoantigen-Specific Strategies to Silence Raucous B Lymphocytes and Halt Cross-Talk with T Cells in Type 1 Diabetes |
| title_fullStr | B Quiet: Autoantigen-Specific Strategies to Silence Raucous B Lymphocytes and Halt Cross-Talk with T Cells in Type 1 Diabetes |
| title_full_unstemmed | B Quiet: Autoantigen-Specific Strategies to Silence Raucous B Lymphocytes and Halt Cross-Talk with T Cells in Type 1 Diabetes |
| title_short | B Quiet: Autoantigen-Specific Strategies to Silence Raucous B Lymphocytes and Halt Cross-Talk with T Cells in Type 1 Diabetes |
| title_sort | b quiet autoantigen specific strategies to silence raucous b lymphocytes and halt cross talk with t cells in type 1 diabetes |
| topic | antibodies autoantigen autoimmunity B cells insulin lymphocytes |
| url | https://www.mdpi.com/2227-9059/9/1/42 |
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