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

Abstract

Abstract Several characteristics of the immunoglobulin (Ig) 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 2 possibilities could explain these differences: (1) fetal and adult lymphocyte progenitors differ significantly in their potential to form a diverse repertoire, and (2) factors extrinsic to the immunoglobulin locus are more influential to the character of the repertoire. To address this we used nonobese diabetic-severe combined immunodeficient-β2 microglobulin knockout (NOD/SCID/β2m-/-) mice reconstituted with human B-cell progenitors to compare the immunoglobulin repertoire potential of human fetal, cord blood, and adult sources. We found nearly identical VH and JH gene segment use and only modest differences in the third complementarity determining region of the immunoglobulin heavy chain (HCDR3). We conclude that the repertoire potential is remarkably similar regardless of the age of the individual from which progenitors are derived. Age-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.