T cell reconstitution by haploidentical BMT does not restore the diversification of the Ig heavy chain gene in patients with X-linked SCID.
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.
Minegishi
Y
Y
Department of Pediatrics, School of Medicine, Tokyo Medical and Dental University, Japan.
Ishii
N
N
Tsuchida
M
M
Okawa
H
H
Sugamura
K
K
Yata
J
J
D001483:Base Sequence; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002455:Cell Division; D002675:Child, Preschool; D008040:Genetic Linkage; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014960:X Chromosome
D007143:Immunoglobulin Heavy Chains