Contribution of VH gene replacement to the primary B cell repertoire

Zhixin Zhang, Michael Zemlin, Yui Hsi Wang, Delicia Munfus, Leslie E. Huye, Harry W. Findley, S. Louis Bridges, David B. Roth, Peter D. Burrows, Max D. Cooper

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

VH replacement has been proposed as one way to modify unwanted antibody specificities, but analysis of this mechanism has been limited without a dynamic cellular model. We describe a human cell line that spontaneously undergoes serial VH gene replacement mediated by cryptic recombination signal sequences (cRSS) located near the 3′ end of VH genes. Recombination-activating gene products, RAG-1 and RAG-2, bind and cleave the cRSS to generate DNA deletion circles during the VH replacement process. A VH replacement contribution to normal repertoire development is revealed by the identification of VH replacement "footprints" in IgH sequences and double-stranded DNA breaks at VH cRSS sites in immature B cells. Surprisingly, the residual 3′ sequences of replaced VH genes contribute charged amino acids to the CDR3 region, a hallmark of autoreactive antibodies.

Original languageEnglish (US)
Pages (from-to)21-31
Number of pages11
JournalImmunity
Volume19
Issue number1
DOIs
StatePublished - Jul 1 2003

Fingerprint

Genetic Recombination
B-Lymphocytes
Protein Sorting Signals
Genes
RAG-1 Genes
B-Lymphoid Precursor Cells
Antibody Specificity
Double-Stranded DNA Breaks
Amino Acids
Cell Line
Antibodies
DNA

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Zhang, Z., Zemlin, M., Wang, Y. H., Munfus, D., Huye, L. E., Findley, H. W., ... Cooper, M. D. (2003). Contribution of VH gene replacement to the primary B cell repertoire. Immunity, 19(1), 21-31. https://doi.org/10.1016/S1074-7613(03)00170-5

Contribution of VH gene replacement to the primary B cell repertoire. / Zhang, Zhixin; Zemlin, Michael; Wang, Yui Hsi; Munfus, Delicia; Huye, Leslie E.; Findley, Harry W.; Bridges, S. Louis; Roth, David B.; Burrows, Peter D.; Cooper, Max D.

In: Immunity, Vol. 19, No. 1, 01.07.2003, p. 21-31.

Research output: Contribution to journalArticle

Zhang, Z, Zemlin, M, Wang, YH, Munfus, D, Huye, LE, Findley, HW, Bridges, SL, Roth, DB, Burrows, PD & Cooper, MD 2003, 'Contribution of VH gene replacement to the primary B cell repertoire', Immunity, vol. 19, no. 1, pp. 21-31. https://doi.org/10.1016/S1074-7613(03)00170-5
Zhang Z, Zemlin M, Wang YH, Munfus D, Huye LE, Findley HW et al. Contribution of VH gene replacement to the primary B cell repertoire. Immunity. 2003 Jul 1;19(1):21-31. https://doi.org/10.1016/S1074-7613(03)00170-5
Zhang, Zhixin ; Zemlin, Michael ; Wang, Yui Hsi ; Munfus, Delicia ; Huye, Leslie E. ; Findley, Harry W. ; Bridges, S. Louis ; Roth, David B. ; Burrows, Peter D. ; Cooper, Max D. / Contribution of VH gene replacement to the primary B cell repertoire. In: Immunity. 2003 ; Vol. 19, No. 1. pp. 21-31.
@article{0ca9a6e789934dd8a9daf53d7363acbc,
title = "Contribution of VH gene replacement to the primary B cell repertoire",
abstract = "VH replacement has been proposed as one way to modify unwanted antibody specificities, but analysis of this mechanism has been limited without a dynamic cellular model. We describe a human cell line that spontaneously undergoes serial VH gene replacement mediated by cryptic recombination signal sequences (cRSS) located near the 3′ end of VH genes. Recombination-activating gene products, RAG-1 and RAG-2, bind and cleave the cRSS to generate DNA deletion circles during the VH replacement process. A VH replacement contribution to normal repertoire development is revealed by the identification of VH replacement {"}footprints{"} in IgH sequences and double-stranded DNA breaks at VH cRSS sites in immature B cells. Surprisingly, the residual 3′ sequences of replaced VH genes contribute charged amino acids to the CDR3 region, a hallmark of autoreactive antibodies.",
author = "Zhixin Zhang and Michael Zemlin and Wang, {Yui Hsi} and Delicia Munfus and Huye, {Leslie E.} and Findley, {Harry W.} and Bridges, {S. Louis} and Roth, {David B.} and Burrows, {Peter D.} and Cooper, {Max D.}",
year = "2003",
month = "7",
day = "1",
doi = "10.1016/S1074-7613(03)00170-5",
language = "English (US)",
volume = "19",
pages = "21--31",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - Contribution of VH gene replacement to the primary B cell repertoire

AU - Zhang, Zhixin

AU - Zemlin, Michael

AU - Wang, Yui Hsi

AU - Munfus, Delicia

AU - Huye, Leslie E.

AU - Findley, Harry W.

AU - Bridges, S. Louis

AU - Roth, David B.

AU - Burrows, Peter D.

AU - Cooper, Max D.

PY - 2003/7/1

Y1 - 2003/7/1

N2 - VH replacement has been proposed as one way to modify unwanted antibody specificities, but analysis of this mechanism has been limited without a dynamic cellular model. We describe a human cell line that spontaneously undergoes serial VH gene replacement mediated by cryptic recombination signal sequences (cRSS) located near the 3′ end of VH genes. Recombination-activating gene products, RAG-1 and RAG-2, bind and cleave the cRSS to generate DNA deletion circles during the VH replacement process. A VH replacement contribution to normal repertoire development is revealed by the identification of VH replacement "footprints" in IgH sequences and double-stranded DNA breaks at VH cRSS sites in immature B cells. Surprisingly, the residual 3′ sequences of replaced VH genes contribute charged amino acids to the CDR3 region, a hallmark of autoreactive antibodies.

AB - VH replacement has been proposed as one way to modify unwanted antibody specificities, but analysis of this mechanism has been limited without a dynamic cellular model. We describe a human cell line that spontaneously undergoes serial VH gene replacement mediated by cryptic recombination signal sequences (cRSS) located near the 3′ end of VH genes. Recombination-activating gene products, RAG-1 and RAG-2, bind and cleave the cRSS to generate DNA deletion circles during the VH replacement process. A VH replacement contribution to normal repertoire development is revealed by the identification of VH replacement "footprints" in IgH sequences and double-stranded DNA breaks at VH cRSS sites in immature B cells. Surprisingly, the residual 3′ sequences of replaced VH genes contribute charged amino acids to the CDR3 region, a hallmark of autoreactive antibodies.

UR - http://www.scopus.com/inward/record.url?scp=0038783610&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038783610&partnerID=8YFLogxK

U2 - 10.1016/S1074-7613(03)00170-5

DO - 10.1016/S1074-7613(03)00170-5

M3 - Article

VL - 19

SP - 21

EP - 31

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 1

ER -