Studies on the somatic instability of immunoglobulin genes in vivo and in cultured cells.

Matthew D. Scharff, H. L. Aguila, S. M. Behar, N. C. Chien, R. DePinho, D. L. French, R. R. Pollock, S. U. Shin

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

We have examined the molecular mechanism and impact of somatic diversification on the T15 heavy chain variable region gene in vivo and in vitro. Somatic point mutation appears to be responsible for the changes we have observed in both hybridomas from early and late in the immune response and in the S107 myeloma cell line in culture. By identifying S107 mutants with decreases in antigen binding, we have shown that a single point mutation can cause the loss of binding to the eliciting antigen and the acquisition of binding to another antigen. Furthermore, in this case a point mutation of the T15 heavy chain variable region gene caused the conversion of an important protective antibody to an autoantibody. While the S107 cell line frequently generates both constant and variable region mutants, hybridomas appear to have relatively stable variable region genes and unstable constant region genes which in some cases result in mutants with increased binding.

Original languageEnglish (US)
Pages (from-to)75-90
Number of pages16
JournalImmunological Reviews
Volume96
StatePublished - Apr 1987

Fingerprint

Immunoglobulin Genes
Point Mutation
Cultured Cells
Hybridomas
Antigens
Genes
Cell Line
Gene Conversion
Autoantibodies
Antibodies

ASJC Scopus subject areas

  • Immunology

Cite this

Scharff, M. D., Aguila, H. L., Behar, S. M., Chien, N. C., DePinho, R., French, D. L., ... Shin, S. U. (1987). Studies on the somatic instability of immunoglobulin genes in vivo and in cultured cells. Immunological Reviews, 96, 75-90.

Studies on the somatic instability of immunoglobulin genes in vivo and in cultured cells. / Scharff, Matthew D.; Aguila, H. L.; Behar, S. M.; Chien, N. C.; DePinho, R.; French, D. L.; Pollock, R. R.; Shin, S. U.

In: Immunological Reviews, Vol. 96, 04.1987, p. 75-90.

Research output: Contribution to journalArticle

Scharff, MD, Aguila, HL, Behar, SM, Chien, NC, DePinho, R, French, DL, Pollock, RR & Shin, SU 1987, 'Studies on the somatic instability of immunoglobulin genes in vivo and in cultured cells.', Immunological Reviews, vol. 96, pp. 75-90.
Scharff MD, Aguila HL, Behar SM, Chien NC, DePinho R, French DL et al. Studies on the somatic instability of immunoglobulin genes in vivo and in cultured cells. Immunological Reviews. 1987 Apr;96:75-90.
Scharff, Matthew D. ; Aguila, H. L. ; Behar, S. M. ; Chien, N. C. ; DePinho, R. ; French, D. L. ; Pollock, R. R. ; Shin, S. U. / Studies on the somatic instability of immunoglobulin genes in vivo and in cultured cells. In: Immunological Reviews. 1987 ; Vol. 96. pp. 75-90.
@article{fde3aded96ae44c39e35e3cb5deb0a64,
title = "Studies on the somatic instability of immunoglobulin genes in vivo and in cultured cells.",
abstract = "We have examined the molecular mechanism and impact of somatic diversification on the T15 heavy chain variable region gene in vivo and in vitro. Somatic point mutation appears to be responsible for the changes we have observed in both hybridomas from early and late in the immune response and in the S107 myeloma cell line in culture. By identifying S107 mutants with decreases in antigen binding, we have shown that a single point mutation can cause the loss of binding to the eliciting antigen and the acquisition of binding to another antigen. Furthermore, in this case a point mutation of the T15 heavy chain variable region gene caused the conversion of an important protective antibody to an autoantibody. While the S107 cell line frequently generates both constant and variable region mutants, hybridomas appear to have relatively stable variable region genes and unstable constant region genes which in some cases result in mutants with increased binding.",
author = "Scharff, {Matthew D.} and Aguila, {H. L.} and Behar, {S. M.} and Chien, {N. C.} and R. DePinho and French, {D. L.} and Pollock, {R. R.} and Shin, {S. U.}",
year = "1987",
month = "4",
language = "English (US)",
volume = "96",
pages = "75--90",
journal = "Immunological Reviews",
issn = "0105-2896",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Studies on the somatic instability of immunoglobulin genes in vivo and in cultured cells.

AU - Scharff, Matthew D.

AU - Aguila, H. L.

AU - Behar, S. M.

AU - Chien, N. C.

AU - DePinho, R.

AU - French, D. L.

AU - Pollock, R. R.

AU - Shin, S. U.

PY - 1987/4

Y1 - 1987/4

N2 - We have examined the molecular mechanism and impact of somatic diversification on the T15 heavy chain variable region gene in vivo and in vitro. Somatic point mutation appears to be responsible for the changes we have observed in both hybridomas from early and late in the immune response and in the S107 myeloma cell line in culture. By identifying S107 mutants with decreases in antigen binding, we have shown that a single point mutation can cause the loss of binding to the eliciting antigen and the acquisition of binding to another antigen. Furthermore, in this case a point mutation of the T15 heavy chain variable region gene caused the conversion of an important protective antibody to an autoantibody. While the S107 cell line frequently generates both constant and variable region mutants, hybridomas appear to have relatively stable variable region genes and unstable constant region genes which in some cases result in mutants with increased binding.

AB - We have examined the molecular mechanism and impact of somatic diversification on the T15 heavy chain variable region gene in vivo and in vitro. Somatic point mutation appears to be responsible for the changes we have observed in both hybridomas from early and late in the immune response and in the S107 myeloma cell line in culture. By identifying S107 mutants with decreases in antigen binding, we have shown that a single point mutation can cause the loss of binding to the eliciting antigen and the acquisition of binding to another antigen. Furthermore, in this case a point mutation of the T15 heavy chain variable region gene caused the conversion of an important protective antibody to an autoantibody. While the S107 cell line frequently generates both constant and variable region mutants, hybridomas appear to have relatively stable variable region genes and unstable constant region genes which in some cases result in mutants with increased binding.

UR - http://www.scopus.com/inward/record.url?scp=0023161409&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023161409&partnerID=8YFLogxK

M3 - Article

VL - 96

SP - 75

EP - 90

JO - Immunological Reviews

JF - Immunological Reviews

SN - 0105-2896

ER -