B7 costimulation and autoantigen specificity enable B cells to activate autoreactive T cells

Area of Science:

• Immunology
• Autoimmunity
• Cellular immunology

Background:

• T cell tolerance to self-antigens can be broken, leading to autoimmune diseases.
• B cells can function as antigen-presenting cells (APCs).
• The role of B cells in initiating T cell autoimmunity is not fully understood.

Purpose of the Study:

• To investigate the role of B cells as auto-APCs in activating autoimmune T cell responses.
• To determine the mechanisms by which B cells break T cell tolerance to self-antigens.

Main Methods:

• Mice were immunized with self-cytochrome c (cyt c) or a cryptic self peptide followed by whole cyt c.
• B cell-deficient (mu MT) mice were used to assess the role of B cells.
• Expression of B7-1 and B7-2 costimulatory molecules on B cells was analyzed.
• T cell proliferation and cytokine mRNA expression (IFN-gamma, IL-4, IL-5, IL-10) were measured.
• Adoptive transfer of B cells and anti-B7-2 treatment were employed.

Main Results:

• Mice immunized with self-cyt c alone did not elicit T or B cell responses.
• Priming with a cryptic self peptide followed by whole cyt c induced autoreactive T cells specific to self-cyt c.
• T cell autoimmunity was abrogated in B cell-deficient mice.
• Autoantigen-specific B cells expressing B7-1/B7-2 costimulatory molecules activated T cells to proliferate and produce cytokines.
• B7-negative B cells or non-specific B7-positive B cells failed to activate naive T cells.
• Anti-B7-2 treatment inhibited the in vivo expression of T cell cytokine mRNA.

Conclusions:

• Autoantigen-specific B cells expressing B7 costimulatory molecules play a critical role in initiating autoimmune T cell responses.
• These B cells act as auto-APCs, breaking T cell tolerance to self-antigens.
• Targeting B cell-APC function or B7 costimulation may be a therapeutic strategy for autoimmune diseases.