Recipient B cells are not required for graft-versus-host disease induction

Biol Blood Marrow Transplant. 2010 Sep;16(9):1222-30. doi: 10.1016/j.bbmt.2010.03.015. Epub 2010 Mar 23.

Abstract

Recipient antigen presenting cells (APCs) are required for CD8-mediated graft-versus-host disease (GVHD), and have an important and nonredundant role in CD4-mediated GVHD in mouse major histocompatibility complex-matched allogeneic bone marrow transplantation (alloBMT). However, the precise roles of specific recipient APCs-dendritic cells, macrophages, and B cells-are not well defined. If recipient B cells are important APCs they could be depleted with rituximab, an anti-CD20 monoclonal antibody. On the other hand, B cells can downregulate T cell responses, and consequently, B cell depletion could exacerbate GVHD. Patients with B cell lymphomas undergo allogeneic hematopoietic stem cell transplantation (alloSCT) and many are B-cell-deficient because of prior rituximab. We therefore studied the role of recipient B cells in major histocompatibility complex-matched murine models of CD8- and CD4-mediated GVHD by using recipients genetically deficient in B cells and with antibody-mediated depletion of host B cells. In both CD4- and CD8-dependent models, B cell-deficient recipients developed clinical and pathologic GVHD. However, although CD8-mediated GVHD was clinically less severe in hosts genetically deficient in B cells, it was unaffected in anti-CD20-treated recipients. These data indicate that recipient B cells are not important initiators of GVHD, and that efforts to prevent GVHD by APC depletion should focus on other APC subsets.

Publication types

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

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • B-Lymphocytes / immunology*
  • Bone Marrow Transplantation / immunology*
  • Bone Marrow Transplantation / methods*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / immunology*
  • Humans
  • Major Histocompatibility Complex / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Transplantation, Homologous / methods