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Blood, Vol. 92 No. 8 (October 15), 1998:
pp. 2802-2814
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
Erhan Gokmen,
Frank M. Raaphorst,
David H. Boldt, and
Judy M. Teale
From the Department of Medicine, Division of Hematology, and
Department of Microbiology, The University of Texas Health Science
Center at San Antonio, San Antonio, TX.
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.
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