B cells in chronic graft-versus-host disease

Biol Blood Marrow Transplant. 2015 Jan;21(1):16-23. doi: 10.1016/j.bbmt.2014.10.029. Epub 2014 Nov 12.

Abstract

Chronic graft-versus-host disease (cGVHD) continues to be a common complication of allogeneic hematopoietic stem cell transplantation. Unlike acute graft-versus-host disease, which is mediated almost entirely by donor T cells, the immune pathology of cGVHD is more complex and donor B cells have also been found to play an important role. Recent studies from several laboratories have enhanced our understanding of how donor B cells contribute to this clinical syndrome and this has led to new therapeutic opportunities. Here, Dr Sarantopoulos reviews some of the important mechanisms responsible for persistent B cell activation and loss of B cell tolerance in patients with cGVHD. Dr Blazar describes recent studies in preclinical models that have identified novel B cell-directed agents that may be effective for prevention or treatment of cGVHD. Some B cell-directed therapies have already been tested in patients with cGVHD and Dr Cutler reviews the results of these studies documenting the potential efficacy of this approach. Supported by mechanistic studies in patients and preclinical models, new B cell-directed therapies for cGVHD will now be evaluated in clinical trials.

Keywords: B cell; Chronic graft-versus-host disease; Stem cell transplantation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • B-Cell Activating Factor / genetics
  • B-Cell Activating Factor / immunology
  • B-Cell Activation Factor Receptor / genetics
  • B-Cell Activation Factor Receptor / immunology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / pathology
  • Chronic Disease
  • Gene Expression Regulation, Neoplastic
  • Graft vs Host Disease / genetics
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / prevention & control
  • Graft vs Host Disease / therapy*
  • Hematologic Neoplasms / genetics
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / pathology
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Lymphocyte Activation
  • Mice
  • Rituximab
  • Transplantation, Homologous

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • B-Cell Activating Factor
  • B-Cell Activation Factor Receptor
  • Immunosuppressive Agents
  • TNFRSF13C protein, human
  • TNFSF13B protein, human
  • Rituximab