Reconstitution of the Ig heavy chain CDR3 repertoire after allogeneic haematopoietic stem cell transplantation with myeloablative or reduced-intensity conditioning regimens.
The objective of this study was to investigate B-lymphocyte reconstitution in patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) after myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) regimens. B-lymphocyte reconstitution was studied by monitoring the CDR3 repertoire with spectratyping. We demonstrate a delay in the recovery of the B-lymphocyte repertoire, measured by variation in size distribution of the immunoglobulin H CDR3 in patients conditioned with RIC compared to MAC. We found no general explanation for this finding, but when clinical data for each patient were studied in detail, we could identify a cause for the oligoclonality of the B-lymphocyte repertoire after HSCT with RIC for each of the patients. Older patients and donors, low cell dose at transplantation, relapse, graft-versus-host disease (GVHD) and its treatment as well as cytomegalovirus infection and its treatment are all possible causes for the restriction of the B-lymphocyte repertoire observed in this study. Taken together, reconstitution of the B-lymphocyte repertoire after HSCT is a process dependent on multiple factors and differs between patients. The conditioning regimen may be of importance, but data from this study suggest that individual factors and the various complications occurring after HSCT are more likely to determine the development of the B-lymphocyte repertoire.
Omazic
B
B
Arvid Wretlind Laboratory at the Center for Surgical Sciences, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm,Sweden. brigitta.omazic@cfss.ki.se
Hentschke
P
P
Näsman-Björk
I
I
Mattsson
J
J
Oxelius
V-A
VA
Ringdén
O
O
Barkholt
L
L
Permert
J
J
Lundkvist
I
I
D000208:Acute Disease; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology; D002678:Chimera / Q000276:immunology; D002908:Chronic Disease; D022801:Complementarity Determining Regions / Q000235:genetics*; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007126:Immunoglobulin Allotypes / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous
D022801:Complementarity Determining Regions; D007126:Immunoglobulin Allotypes; D007074:Immunoglobulin G