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VH gene analysis of spontaneously activated B cells in adult MRL-lpr/lpr mice. J558 bias is not limited to classic lupus autoantibodies.

Publication ,  Journal Article
Foster, MH; MacDonald, M; Barrett, KJ; Madaio, MP
Published in: J Immunol
September 1, 1991

To determine the genetic origins of lupus auto-antibodies, we analyzed the relationship between VH 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; VH 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 autoantibodies and nonbinder IgM, used relatively 3' VH genes. The majority of B cells in adult mice used VH 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 VH 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.

Duke Scholars

Published In

J Immunol

ISSN

0022-1767

Publication Date

September 1, 1991

Volume

147

Issue

5

Start / End Page

1504 / 1511

Location

United States

Related Subject Headings

  • Thymus Gland
  • Rabbits
  • Mice
  • Lymphocyte Activation
  • Lupus Erythematosus, Systemic
  • Immunology
  • Immunoglobulin Variable Region
  • Immunoglobulin Isotypes
  • Immunoglobulin Heavy Chains
  • Genes, Immunoglobulin
 

Citation

APA
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ICMJE
MLA
NLM
Foster, M. H., MacDonald, M., Barrett, K. J., & Madaio, M. P. (1991). VH gene analysis of spontaneously activated B cells in adult MRL-lpr/lpr mice. J558 bias is not limited to classic lupus autoantibodies. J Immunol, 147(5), 1504–1511.
Foster, M. H., M. MacDonald, K. J. Barrett, and M. P. Madaio. “VH gene analysis of spontaneously activated B cells in adult MRL-lpr/lpr mice. J558 bias is not limited to classic lupus autoantibodies.J Immunol 147, no. 5 (September 1, 1991): 1504–11.

Published In

J Immunol

ISSN

0022-1767

Publication Date

September 1, 1991

Volume

147

Issue

5

Start / End Page

1504 / 1511

Location

United States

Related Subject Headings

  • Thymus Gland
  • Rabbits
  • Mice
  • Lymphocyte Activation
  • Lupus Erythematosus, Systemic
  • Immunology
  • Immunoglobulin Variable Region
  • Immunoglobulin Isotypes
  • Immunoglobulin Heavy Chains
  • Genes, Immunoglobulin