Ig Heavy Chain Third Complementarity Determining Regions (H CDR3s) After Stem Cell Transplantation Do Not Resemble the Developing Human Fetal H CDR3s in Size Distribution and Ig Gene Utilization

Abstract

Abstract Previous studies have suggested that the B-cell repertoire after stem cell transplantation resembles the developing repertoire in the fetus. Fetal and adult repertoires differ strikingly at the molecular level in Ig heavy chain third complementarity determining region (H CDR3) size distribution and Ig gene utilization. Previously, the posttransplant repertoire has not been studied fully in this regard. In this study, we analyzed H CDR3s posttransplant using CDR3 fingerprinting, single-strand conformation polymorphism (SSCP), and random sequencing. Eleven adult patients who received either autologous (n = 6) or allogeneic adult sibling (n = 5) hematopoietic stem cell transplants were studied. IgM H CDR3 repertoires demonstrated limited clonal diversity within the first 6 to 10 weeks posttransplant. By 3 to 4 months, the IgM H CDR3 repertoires were as diverse as those in healthy adults. Reconstitution of the IgM diversity correlated with the expansion of the multimember VH3 family. By contrast, the contribution of the single-member VH6 family was limited in most patients up to 6 to 9 months. No evidence was seen for greater contribution of VH6 posttransplant. IgG repertoires remained clonally restricted at all times. In all patients, H CDR3 sizes fell within adult limits. Direct nucleotide sequencing of H CDR3s showed adult-type N-nucleotide insertions and Ig gene utilization. These results indicate that the emerging repertoire posttransplant does not resemble the developing fetal repertoire at the molecular level. © 1998 by The American Society of Hematology.