The VlJl Repertoire in Human Fetal Spleen: Evidence for Positive Selection and Extensive Receptor Editing

VlJl rearrangements obtained from genomic DNA of individual IgM B cells from human fetal spleen were analyzed. A nonrandom pattern of l gene rearrangements that differed from the adult Vl repertoire was found. The Vl distal genes 8A and 4B were absent from the nonproductive fetal repertoire, whereas 2E and 3L were overrepresented and 1B was underrepresented in the productive fetal repertoire. Positive selection of the Vl gene, 2E, along with Vl rearrangements employing homologous VlJl joins were observed in the fetal, but not in the adult Vl repertoire. Overrepresentation of Jl distal cluster C genes rearranging to the Vl distal J segment, Jl7, in both productive and nonproductive fetal repertoires suggested that receptor editing/replacement was more active in the fetus than in adults. Numerous identical VlJl junctions were observed in both the productive and nonproductive repertoire of the fetus and adult, but were significantly more frequent in the productive repertoire of the fetus, suggesting expansion of B cells expressing particular l-light chains in both stages of development, with more profound expansion in the fetal repertoire. Notably, B cells expressing identical l-light chains expressed diverse heavy chains. These data demonstrate that three mechanisms strongly influence the shaping of the human fetal l-chain repertoire that are less evident in the adult: positive selection, receptor editing, and expansion of B cells expressing specific l-light chains. These events imply that the expressed fetal repertoire is shaped by exposure to self Ags. The Journal of Immunology, 2000, 165: 6322–6333.