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Immunoglobulin heavy chain variable region gene usage in bone marrow
transplant recipients: lack of somatic mutation indicates a maturational
arrest [see comments]
I Suzuki, EC Milner, AM Glas, WO Hufnagle, SP Rao, L Pfister and C Nottenburg
Virginia Mason Research Center, Seattle, WA, USA.
Many recipients of bone marrow transplant (BMT) make normal amounts of
serum immunoglobulin but are deficient in generating specific antibody
responses to exogenous stimuli. To determine if abnormal usage of VH genes
contributes to this immunodeficiency, the usage of VH genes was determined
in peripheral blood B cells of four BMT recipients, two of whom had
developed chronic graft versus host disease. The pattern of usage of VH3 or
VH4 genes assessed at either 90 days or approximately 1 year after
transplant was similar to that observed in healthy subjects and was marked
by the over utilization of two elements, one VH3 and one VH4. However, the
repertoires of each of the four BMT recipients appeared to be less complex
than the repertoires of healthy subjects. The differences were a
consequence of the accumulation of somatic mutations among rearrangements
in the controls but not in the BMT recipients. The failure to accumulate
somatic mutations in rearranged VH genes is consistent with a defect in
antigen driven B-cell responses. These results indicate the although the VH
gene content of the repertoire has normalized by 90 days posttransplant, a
maturational arrest in B-cell differentiation associated with antigen
activation persists for at least 1 year after BMT.
Volume 87,
Issue 5,
pp. 1873-1880,
03/01/1996
Copyright © 1996 by The American Society of Hematology
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