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Mice lacking endogenous IL-10-producing regulatory B cells develop exacerbated disease and present with an increased

Natalie A Carter1, Rita Vasconcellos, Elizabeth C Rosser

  • 1Division of Medicine, Centre for Rheumatology Research, University College London, London W1T 4JF, United Kingdom.

Journal of Immunology (Baltimore, Md. : 1950)
|April 6, 2011
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Regulatory B cells (Bregs) producing IL-10 are crucial for controlling autoimmune diseases like arthritis. Lacking these Bregs exacerbates arthritis by reducing regulatory T cells (Tregs) and increasing inflammatory T cells.

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Area of Science:

  • Immunology
  • Autoimmunity
  • Cell Biology

Background:

  • Interleukin-10 (IL-10)-producing B cells, termed regulatory B cells (Bregs), are critical for immune homeostasis.
  • Dysregulation of Bregs is implicated in the pathogenesis of autoimmune diseases.

Purpose of the Study:

  • To investigate the specific role of IL-10-producing B cells in regulating T cell responses and controlling arthritis.
  • To identify the B cell subset responsible for modulating regulatory T cell (Treg) populations.

Main Methods:

  • Chimeric mice lacking IL-10-producing B cells were generated and compared to wild-type controls.
  • Flow cytometry was used to analyze T cell populations (Tregs, Th1, Th17) in different mouse models.
  • B cell subsets were transferred into B cell-deficient mice to assess their immunomodulatory capacity in vitro and in vivo.

Main Results:

  • Mice lacking IL-10-producing B cells exhibited exacerbated arthritis, decreased Foxp3+ regulatory T cell numbers and expression, and increased inflammatory Th1/Th17 cells.
  • Transitional 2 marginal zone precursor Bregs were identified as the exclusive B cell subset capable of modulating Treg frequencies.
  • Transfer of these specific Bregs restored Treg levels, reduced inflammatory T cells, and ameliorated arthritis in IL-10(-/-) mice.
  • In vitro studies showed IL-10-producing B cells enhanced T cell contact time and promoted Foxp3 upregulation on T cells.

Conclusions:

  • IL-10-producing B cells, particularly transitional 2 marginal zone precursor Bregs, are essential for restraining autoimmune inflammation.
  • These Bregs exert their regulatory function by promoting the differentiation of immunoregulatory T cells over pro-inflammatory T cell subsets.