IMMUNOGLOBULIN HEAVY-CHAIN VARIABLE REGION GENE USAGE IN BONE-MARROW TRANSPLANT RECIPIENTS - LACK OF SOMATIC MUTATION INDICATES A MATURATIONAL ARREST

Many recipients of bone marrow transplant (BMT) make normal amounts of serum immunoglobulin but are deficient in generating specific antibod y responses to exogenous stimuli. To determine if abnormal usage of V- H genes contributes to this immunodeficiency, the usage of V-H genes w as determined in peripheral blood B cells of four BMT recipients, two of whom had developed chronic graft versus host disease. The pattern o f usage of V(H)3 or V(H)4 genes assessed at either 90 days or approxim ately 1 year after transplant was similar to that observed in healthy subjects and was marked by the over utilization of two elements, one V (H)3 and one V(H)4. However, the repertoires of each of the four BMT r ecipients appeared to be less complex than the repertoires of healthy subjects. The differences were a consequence of the accumulation of so matic mutations among rearrangements in the controls but not in the BM T recipients. The failure to accumulate somatic mutations in rearrange d V-H genes is consistent with a defect in antigen driven B-cell respo nses. These results indicate that although the V-H gene content of the repertoire has normalized by 90 days posttransplant, a maturational a rrest in B-cell differentiation associated with antigen activation per sists for at least 1 year after BMT. (C) 1996 by The American Society of Hematology.