Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Feb 25;15(3):332.
doi: 10.3390/biom15030332.

Dia-B-Ties: B Cells in the Islet-Immune-Cell Interface in T1D

Brandon K Hilliard  1   2 , Jessica E Prendergast  1   2 , Mia J Smith  1   2
Affiliations
Review

Dia-B-Ties: B Cells in the Islet-Immune-Cell Interface in T1D

Brandon K Hilliard et al. Biomolecules. .

Abstract

Type 1 diabetes (T1D) is an autoimmune disease that affects an estimated 30 million people worldwide and results in a lifelong dependency of exogenous insulin treatments. While T1D is characterized by T-cell driven-destruction of the insulin-secreting β cells, B lymphocytes play a key role in the islet-immune interface. B cells are an essential intermediary between islet cells and other immune-cell populations. Through antigen presentation, cytokine secretion, and antibody production, B cells play a role in activating autoreactive islet-specific T cells, thus potentiating pancreatic inflammation in the early stages of T1D. Despite this, their role in disease development remains an understudied feature of T1D with significant therapeutic potential. Herein, we will discuss the current knowledge of the islet-immune-cell interface within T1D through the lens of B lymphocytes. We will also consider knowledge gaps that may be limiting further therapeutic opportunities.

Keywords: B cells; B lymphocytes; antigen-presenting cells; autoantibodies; insulitis; type 1 diabetes.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Effector functions of B cells in T1D pathogenesis. (A) B Antigen to CD4+ and CD8+ T cells, (B) autoantibody production, and (C) cytokine production by B cells.
Figure 2
Figure 2
Pathological function of B cells in T1D development. (A) Autoantibodies, while not the primary drivers of β cell destruction, also have the capacity to potentiate β cell destruction. Through Fc receptors on the cell surface of professional antigen-presenting cells (APCs), such as dendritic cells and macrophages, APCs can enhance the activation of autoreactive T cells through Fc-mediated uptake of islet antigen–antibody complexes that are, in turn, presented to self-reactive T cells. (B) B cells can present antigen bound by their respective BCRs to CD4 T cells. Additionally, B cells can present antigen to CD8 T cells through cross-presentation. Following activation by B cells, CD4 and CD8 T cells are the primary effector cells in pancreatic β-cell destruction. (C) B cells can produce various pro-inflammatory cytokines, including TNFα, IL1β, IL6, and IFN-γ. These cytokines contribute to T1D pathogenesis by increasing MHC I expression on the surface of β cells, enhancing recruitment of T cells to the site of inflammation (i.e., pancreas), and contributing to an increased apoptotic response of β cells.
Figure 3
Figure 3
Direct comparison of human and rodent islet architecture. Human islets cell populations are intermixed among each other. Rodent islets have a core of β cells surrounded by the α, δ, and PP cells.
Figure 4
Figure 4
B-cell depletion therapies. (A) Antigen-agnostic B-cell depletion therapies; (B) antigen-specific B-cell depletion therapies.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Atkinson M.A. The Pathogenesis and Natural History of Type 1 Diabetes. Cold Spring Harb. Perspect. Med. 2012;2:a007641. doi: 10.1101/cshperspect.a007641. - DOI - PMC - PubMed
    1. Pambianco G., Costacou T., Ellis D., Becker D.J., Klein R., Orchard T.J. The 30-year natural history of type 1 diabetes complications: The Pittsburgh Epidemiology of Diabetes Complications Study experience. Diabetes. 2006;55:1463–1469. doi: 10.2337/db05-1423. - DOI - PubMed
    1. Smith M.J., Boldison J., Wong F.S. The Role of B Lymphocytes in Type 1 Diabetes. Cold Spring Harb. Perspect. Med. 2024:a041593. doi: 10.1101/cshperspect.a041593. - DOI - PubMed
    1. Roep B.O. The role of T-cells in the pathogenesis of Type 1 diabetes: From cause to cure. Diabetologia. 2003;46:305–321. doi: 10.1007/s00125-003-1089-5. - DOI - PubMed
    1. Akashi T., Nagafuchi S., Anzai K., Kondo S., Kitamura D., Wakana S., Ono J., Kikuchi M., Niho Y., Watanabe T. Direct evidence for the contribution of B cells to the progression of insulitis and the development of diabetes in non-obese diabetic mice. Int. Immunol. 1997;9:1159–1164. doi: 10.1093/intimm/9.8.1159. - DOI - PubMed

MeSH terms

LinkOut - more resources