TY - JOUR
T1 - The VλJλ repertoire in human fetal spleen
T2 - Evidence for positive selection and extensive receptor editing
AU - Lee, J.
AU - Monson, N. L.
AU - Lipsky, P. E.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2000/12/1
Y1 - 2000/12/1
N2 - VλJλ rearrangements obtained from genomic DNA of individual IgM+ B cells from human fetal spleen were analyzed. A nonrandom pattern of λ gene rearrangements that differed from the adult Vλ repertoire was found. The Vλ 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 Vλ gene, 2E, along with Vλ rearrangements employing homologous VλJλ joins were observed in the fetal, but not in the adult Vλ repertoire. Overrepresentation of Jλ distal cluster C genes rearranging to the Vλ distal J Segment, Jλ7, in both productive and nonproductive fetal repertoires suggested that receptor editing/replacement was more active in the fetus than in adults. Numerous identical VλJλ 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 λ-light chains in both stages of development, with more profound expansion in the fetal repertoire. Notably, B cells expressing identical λ-light chains expressed diverse heavy chains. These data demonstrate that three mechanisms strongly influence the shaping of the human fetal λ-chain repertoire that are less evident in the adult: positive selection, receptor editing, and expansion of B cells expressing specific λ-light chains. These events imply that the expressed fetal repertoire is shaped by exposure to self Ags.
AB - VλJλ rearrangements obtained from genomic DNA of individual IgM+ B cells from human fetal spleen were analyzed. A nonrandom pattern of λ gene rearrangements that differed from the adult Vλ repertoire was found. The Vλ 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 Vλ gene, 2E, along with Vλ rearrangements employing homologous VλJλ joins were observed in the fetal, but not in the adult Vλ repertoire. Overrepresentation of Jλ distal cluster C genes rearranging to the Vλ distal J Segment, Jλ7, in both productive and nonproductive fetal repertoires suggested that receptor editing/replacement was more active in the fetus than in adults. Numerous identical VλJλ 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 λ-light chains in both stages of development, with more profound expansion in the fetal repertoire. Notably, B cells expressing identical λ-light chains expressed diverse heavy chains. These data demonstrate that three mechanisms strongly influence the shaping of the human fetal λ-chain repertoire that are less evident in the adult: positive selection, receptor editing, and expansion of B cells expressing specific λ-light chains. These events imply that the expressed fetal repertoire is shaped by exposure to self Ags.
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U2 - 10.4049/jimmunol.165.11.6322
DO - 10.4049/jimmunol.165.11.6322
M3 - Article
C2 - 11086069
AN - SCOPUS:0034541166
SN - 0022-1767
VL - 165
SP - 6322
EP - 6333
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -