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J Repertoire in Human Fetal Spleen: Evidence for Positive Selection and Extensive Receptor Editing1
Department of Internal Medicine and Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75235
V
J rearrangements obtained from genomic DNA of individual
IgM+ B cells from human fetal spleen were analyzed. A
nonrandom pattern of gene rearrangements that differed from the
adult V repertoire was found. The V 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 V gene, 2E, along with V
rearrangements employing homologous VJ joins were observed in the
fetal, but not in the adult V repertoire. Overrepresentation of J
distal cluster C genes rearranging to the V distal J segment, J7,
in both productive and nonproductive fetal repertoires suggested that
receptor editing/replacement was more active in the fetus than in
adults. Numerous identical VJ 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 -light
chains in both stages of development, with more profound expansion in
the fetal repertoire. Notably, B cells expressing identical -light
chains expressed diverse heavy chains. These data demonstrate that
three mechanisms strongly influence the shaping of the human fetal
-chain repertoire that are less evident in the adult: positive
selection, receptor editing, and expansion of B cells expressing
specific -light chains. These events imply that the expressed fetal
repertoire is shaped by exposure to self Ags.
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