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The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
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B cells enable autoreactive T cells to avoid suppression.

Matthew Funsten1,2, Renee de Pooter1, Vineeth Varanasi1

  • 1Department of Pathology, The University of Chicago, Chicago, IL 60637.

Proceedings of the National Academy of Sciences of the United States of America
|April 9, 2026
PubMed
Summary
This summary is machine-generated.

B cells promote organ-specific autoimmunity by activating T effector cells (Teff) while evading suppression from regulatory T cells (Treg). This highlights B cells as therapeutic targets for autoimmune diseases.

Keywords:
B cellsTregsorgan-specific autoimmunity

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Area of Science:

  • Immunology
  • Autoimmunity Research
  • Cellular Immunology

Background:

  • B cells are crucial in developing T cell-mediated organ-specific autoimmunity.
  • The precise role of B cells in this process remains unclear.
  • B cell antigen presentation is specific to their receptors, influencing T cell activation dynamics.

Purpose of the Study:

  • To elucidate the differential roles of B cells and dendritic cells (DCs) in T effector cell (Teff) and regulatory T cell (Treg) activation.
  • To investigate how B cell-specific antigen presentation affects Treg-mediated suppression compared to DC presentation.
  • To provide evidence supporting anti-B cell immunotherapies for autoimmune conditions.

Main Methods:

  • Utilized Teff cells (KRN) and B cells (121) specific for glucose-6-phosphate-isomerase (GPI).
  • Assessed the sensitivity of KRN T cell activation to polyclonal Tregs when presented by DCs versus B cells.
  • Evaluated the suppressive capacity of GPI-specific Tregs against Teff activation mediated by B cells.

Main Results:

  • Teff activation by DCs was sensitive to polyclonal Treg suppression.
  • Teff activation by B cells was resistant to polyclonal Treg suppression.
  • GPI-specific Tregs effectively suppressed Teff activation when presented by B cells.

Conclusions:

  • B cells preferentially activate Teff cells without significant suppression by bystander Tregs, unlike DCs.
  • The specificity of B cell antigen presentation contributes to their role in driving autoimmunity.
  • Findings support the therapeutic targeting of B cells in organ-specific autoimmune diseases.