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Evidence for oligoclonal diversification of the VH6-containing
immunoglobulin repertoire during reconstitution after bone marrow
transplantation
I Nasman and I Lundkvist
Department of Immunology, Microbiology, Pathology, and Infectious Diseases,
Karolinska Institutet at Huddinge University Hospital, Sweden.
Patients who have undergone bone marrow transplantation (BMT) remain
immunodeficient for months to years posttransplantation. To evaluate the
basic molecular events underlying reconstitution of the humoral immune
response, we have performed a detailed nucleotide sequence analysis of VH6
containing rearrangements in circulating B cells from two BM
donor/recipient pairs. Our results show that the third complementarity
determining region (CDR3) diversity is much lower early after
transplantation, compared with that of the donors, and that the clonal
variability remains low for 3 months. Repertoire diversification follows an
oligoclonal pattern where B lymphopoiesis appears to occur in waves up to 6
months posttransplantation. The repertoire among donated marrow cells is
not reflected in peripheral blood lymphocytes from the transplanted
patients. There is differential D gene utilization among both donor and
patient samples, whereas JH gene usage is biased toward JH4, 5, and 6. One
month after transplantation the vast majority of the sequenced clones are
functional and contain a high frequency of replacement mutations in the
CDRs of the VH6 gene. We conclude that Ig gene expression is very
restricted early after BMT and that development of the B-cell repertoire
appears to follow a wavelike pattern.
Volume 87,
Issue 7,
pp. 2795-2804,
04/01/1996
Copyright © 1996 by The American Society of Hematology
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