T cell reconstitution by haploidentical BMT does not restore the diversification of the Ig heavy chain gene in patients with X-linked SCID
Minegishi, Y.; Ishii, N.; Tsuchida, M.; Okawa, H.; Sugamura, K.; Yata, J.
Bone Marrow Transplantation 16(6): 801-806
1995
ISSN/ISBN: 0268-3369 PMID: 8750273 Document Number: 441648
We previously examined the Ig heavy (H) chain gene of pretransplant patients with X-linked SCID (XSCID), having defects in the gene of the IL-2 receptor (R) gamma chain. In the present study, we analyzed two post-transplant XSCID patients, in whom T cell-depleted haploidentical BMT resulted in lymphoid split chimeras, i.e., donor functional T cells coexisting with recipient B cells. Although the recipient B cells produced IgM, no isohemagglutinin or Ag-specific Ab was detected. To investigate the cause of failure to produce Ab in the patients, we sequenced the complementarity determining region 3 (CDR3) and adjacent region of Ig H chain gene, which govern Ab specificity. Among the 64 post-transplant CDR3 junctional sequences, combinatorial and junctional diversity were normal compared with those in age-matched controls. All of the post-transplant joining regions except one clone were equal to germline and the frequency of somatic mutation was significantly lower than that in age-matched controls. The results indicated that T cell reconstitution by BMT does not restore diversification of the Ig gene in the IL-2R gamma chain-deficient B cells, which might be associated with the defect in the Ag-specific Ab production.