V(H) gene analysis of spontaneously activated B cells in adult MRL-lpr/lpr mice

J558 bias is not limited to classic lupus autoantibodies

M. H. Foster, M. MacDonald, K. J. Barrett, Michael P. Madaio

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

To determine the genetic origins of lupus auto-antibodies, we analyzed the relationship between V(H) gene usage and auto-Ag-binding properties of 352 B cell hybridomas derived from MRL-lpr/lpr mice. The hybridomas were derived from neonatal, 1-month-old, 3-month-old, and 6-month-old mice. The experimental strategy provided that the hybridomas were monoclonal at initial evaluation, so the Ag binding and V gene frequencies of the entire population could be determined. Initially, 1032 Ig-producing hybridomas were evaluated for binding to six Ag; V(H) gene family use was determined in 119 anti-DNA and anti-rabbit thymus extract (RTE) antibodies (autoantibodies) and in 233 age-matched Ig that did not bind to any of the six Ag (nonbinders). Neonatal B cells, including cross-reactive IgM auto-antibodies and nonbinder IgM, used relatively 3' V(H) genes. The majority of B cells in adult mice used V(H) genes of the J558 family. Although J558 use was significantly higher among the autoantibodies (anti-DNA and anti-RTE) than among the nonbinder Ig, this difference was due to a higher frequency of J558 use by 1-month-old mice. At 3 months, J558 use by the nonbinder Ig increased to the same frequency of J558 use as in the autoantibody population. J558 use in both groups of antibodies exceeded a previously reported estimation of J558 expression in the functional B cell repertoire of young adult MRL-lpr/lpr mice. Several subgroups of antibodies that share properties with pathogenic Ig, including IgG, cross-reactive Ig, and anti-dsDNA autoantibodies, demonstrated a marked preferential expression of the J558 family. These results suggest that there is an age-related bias in the activation of B cells using J558 V(H) genes in MRL-lpr/lpr mice that is under the influence of a selective force distinct from, or in addition to, an ssDNA or RTE auto-Ag-driven response.

Original languageEnglish (US)
Pages (from-to)1504-1511
Number of pages8
JournalJournal of Immunology
Volume147
Issue number5
StatePublished - Jan 1 1991
Externally publishedYes

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Autoantibodies
B-Lymphocytes
Thymus Extracts
Hybridomas
Genes
Rabbits
Immunoglobulin M
DNA
Gene Frequency
Population
Young Adult
Immunoglobulin G

ASJC Scopus subject areas

  • Immunology

Cite this

V(H) gene analysis of spontaneously activated B cells in adult MRL-lpr/lpr mice : J558 bias is not limited to classic lupus autoantibodies. / Foster, M. H.; MacDonald, M.; Barrett, K. J.; Madaio, Michael P.

In: Journal of Immunology, Vol. 147, No. 5, 01.01.1991, p. 1504-1511.

Research output: Contribution to journalArticle

Foster, M. H. ; MacDonald, M. ; Barrett, K. J. ; Madaio, Michael P. / V(H) gene analysis of spontaneously activated B cells in adult MRL-lpr/lpr mice : J558 bias is not limited to classic lupus autoantibodies. In: Journal of Immunology. 1991 ; Vol. 147, No. 5. pp. 1504-1511.
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abstract = "To determine the genetic origins of lupus auto-antibodies, we analyzed the relationship between V(H) gene usage and auto-Ag-binding properties of 352 B cell hybridomas derived from MRL-lpr/lpr mice. The hybridomas were derived from neonatal, 1-month-old, 3-month-old, and 6-month-old mice. The experimental strategy provided that the hybridomas were monoclonal at initial evaluation, so the Ag binding and V gene frequencies of the entire population could be determined. Initially, 1032 Ig-producing hybridomas were evaluated for binding to six Ag; V(H) gene family use was determined in 119 anti-DNA and anti-rabbit thymus extract (RTE) antibodies (autoantibodies) and in 233 age-matched Ig that did not bind to any of the six Ag (nonbinders). Neonatal B cells, including cross-reactive IgM auto-antibodies and nonbinder IgM, used relatively 3' V(H) genes. The majority of B cells in adult mice used V(H) genes of the J558 family. Although J558 use was significantly higher among the autoantibodies (anti-DNA and anti-RTE) than among the nonbinder Ig, this difference was due to a higher frequency of J558 use by 1-month-old mice. At 3 months, J558 use by the nonbinder Ig increased to the same frequency of J558 use as in the autoantibody population. J558 use in both groups of antibodies exceeded a previously reported estimation of J558 expression in the functional B cell repertoire of young adult MRL-lpr/lpr mice. Several subgroups of antibodies that share properties with pathogenic Ig, including IgG, cross-reactive Ig, and anti-dsDNA autoantibodies, demonstrated a marked preferential expression of the J558 family. These results suggest that there is an age-related bias in the activation of B cells using J558 V(H) genes in MRL-lpr/lpr mice that is under the influence of a selective force distinct from, or in addition to, an ssDNA or RTE auto-Ag-driven response.",
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