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Blood, 1 November 2004, Vol. 104, No. 9, pp. 2981-2987.
Prepublished online as a Blood First Edition Paper on July 15, 2004; DOI 10.1182/blood-2003-11-3961.


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Submitted November 19, 2003
Accepted June 21, 2004

Human fetal, cord blood, and adult lymphocyte progenitors have similar potential for generating B cells with a diverse immunoglobulin repertoire

Grant R Kolar, Takafumi Yokota, Maria Isabel D Rossi, Swapan K Nath, and J D Capra*

Program in Molecular Immunogenetics, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA; Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
Program in Immunobiology and Cancer, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
Program in Arthritis and Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA

* Corresponding author; email: donald-capra{at}omrf.ouhsc.edu.

Several characteristics of the immunoglobulin repertoire in fetuses and adults set them apart from each other. Functionally, this translates into differences in the affinity and effectiveness of the humoral immune response between adults and the very young. At least two possibilities could explain these differences: (1) fetal and adult lymphocyte progenitors differ significantly in the recombination potential of the immunoglobulin locus, and (2) factors extrinsic to the immunoglobulin locus are more influential to the character of the repertoire. To address this we used NOD/SCID/{beta}2m-/- mice reconstituted with human B cell progenitors to compare the immunoglobulin repertoire potential of human fetal and adult sources. We found nearly identical VH and JH gene segment utilization and modest differences in HCDR3 characteristics. We conclude that the repertoire potential was remarkably similar regardless of the age of the individual from which progenitors are derived. Aging related differences in the immunoglobulin repertoire and variance of B cell responses to immunization appear to arise from selection rather than from changes in recombination of the immunoglobulin locus itself. From the standpoint of the Ig repertoire, an immune system reconstituted from fetal or neonatal stem cells would likely be as diverse as one generated from adult bone marrow.


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