VH1 Family Immunoglobulin Repertoire Sequencing after Allogeneic Hematopoietic Stem Cell Transplantation

PLoS One. 2017 Jan 17;12(1):e0168096. doi: 10.1371/journal.pone.0168096. eCollection 2017.

Abstract

After allogeneic hematopoietic stem cell transplantation (HSCT), recovery of humoral immunity is essential to protect from life-threatening infections. However, monitoring the humoral immune system after transplantation with standard techniques in the clinical routine is imprecise. Here, we performed sequencing of mononuclear bone marrow cells to characterize the VH1-repertoire of switched B cells of healthy volunteers and patients undergoing HSCT. Analysis of healthy bone marrow donors and patients showed virtually no clonally related sequences between individuals. Interestingly, clonally related sequences were present in pre- and post-transplantation bone marrow of patients undergoing HSCT for acute myeloid leukemia treatment. We consistently observed such related B cell clones, irrespective of conditioning regimen, donor source or time post transplantation. In general, repertoire diversity was lower in post-HSCT as compared to pre-HSCT samples. However, post-HSCT repertoires retained highly mutated sequences, despite immunosuppressive therapy and presence of T cell deficiency after HSCT. These observations identify key properties of the recovering B cell compartment and provide a conceptual framework for the surveillance of humoral immunity after allogeneic transplantation.

MeSH terms

  • Adult
  • Aged
  • Female
  • Genes, Immunoglobulin Heavy Chain / genetics*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunoglobulin Variable Region / genetics*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Middle Aged
  • Sequence Analysis, DNA
  • Transplantation, Homologous
  • Young Adult

Substances

  • Immunoglobulin Variable Region

Grants and funding

This work was supported by Deutsche Forschungsgemeinschaft (www.dfg.de): SFB900-B08 (to CK) and PA921/4-1 (to OP), and Deutsches Zentrum für Infektionsforschung (www.dzif.de) (to OP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.