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Molecular Medicine

, Volume 18, Issue 1, pp 123–137 | Cite as

Multiple Mechanisms of Immune Suppression by B Lymphocytes

  • Matthew W. Klinker
  • Steven K. Lundy
Invited Review Article

Abstract

Suppression of the immune system after the resolution of infection or inflammation is an important process that limits immune-mediated pathogenesis and autoimmunity. Several mechanisms of immune suppression have received a great deal of attention in the past three decades. These include mechanisms related to suppressive cytokines, interleukin (IL)-10 and transforming growth factor (TGF)-β, produced by regulatory cells, and mechanisms related to apoptosis mediated by death ligands, Fas ligand (FasL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), expressed by killer or cytotoxic cells. Despite many lines of evidence supporting an important role for B lymphocytes as both regulatory and killer cells in many inflammatory settings, relatively little attention has been given to understanding the biology of these cells, their relative importance or their usefulness as therapeutic targets. This review is intended to give an overview of the major mechanisms of immunosuppression used by B lymphocytes during both normal and inflammatory contexts. The more recent discoveries of expression of granzyme B, programmed death 1 ligand 2 (PD-L2) and regulatory antibody production by B cells as well as the interactions of regulatory and killer B cells with regulatory T cells, natural killer T (NKT) cells and other cell populations are discussed. In addition, new evidence on the basis of independent characterizations of regulatory and killer CD5+ B cells point toward the concept of a multipotent suppressor B cell with seemingly high therapeutic potential.

Notes

Acknowledgments

The authors wish to thank Dr. David Fox for critical review of the manuscript and Julie Olivero for administrative assistance. Financial support for MW Klinker was received from the Rackham Graduate School Merit Fellowship Program and Immunology Training Program grant from the National Institutes of Health (NIH). SK Lundy received support from the Edward T. and Ellen K. Dryer Foundation, the Arthritis Foundation and the NIH-National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (5-K01-AR-053846). Additional support was received from the University of Michigan Rheumatic Diseases Core Center (grant NIH-NIAMS P30-AR-048310).

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Authors and Affiliations

  1. 1.Department of Internal Medicine, Division of RheumatologyUniversity of Michigan Medical SchoolAnn ArborUSA

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