Specificity and molecular characteristics of monoclonal IgM rheumatoid factors from arthritic and non-arthritic mice

M. T. Aguado, R. S. Balderas, R. L. Rubin, M. A. Duchosal, R. Kofler, B. K. Birshtein, D. S. Secher, F. J. Dixon, A. N. Theofilopoulos

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Abstract

Two-hundred twenty-four hybridomas secreting monoclonal IgM rheumatoid factor (hIgMRF) derived from MRL-lpr/lpr, MRL-+/+ and C57BL/6-lpr/lpr autoimmune mice were analyzed with regard to IgG subclass and domain specificity, and some for V(H) gene expression patterns. Among these mice, only MRL-lpr/lpr develop arthritis. Clonotypes specific for each of the four mouse IgG subclasses and clonotypes reacting with more than one IgG subclass were identified. Although each panel contained several clonotypes, the predominant one differed in each strain (MRL-lpr/lpr, anti-IgG2a; MRL-+/+, combined anti-IgG2a and 2b; C57BL/6-lpr/lpr, anti-IgG1 or combined anti-IgG1, 2a, and 3). The IgG domains recognized by these monoclonals were defined with mutant Ig carrying IgG1 heavy chains that lacked either the CH1 or CH3 domains, variant Ig carrying hybrid IgG2b-2a heavy chains, and IgG fragments. Inhibition of hIgMRF binding to IgG substrates by protein A was also assessed. Most determinants were assigned to the CH3 domain, but determinants in the hinge region, CH2 domain, and in some instances, even in the Fab portion, could also be identified. Hybridization of cytoplasmic RNA from 35 clones of diverse IgG subclass specificity with V(H) gene probes representing seven of the approximately 10 V(H) families (7183, S107, Q52, J558, J606, 36-60, X24) indicated that ~90% of these clones expressed V(H) genes belonging to the large J558 gene family. The results indicate that a) murine IgMRF are extremely heterogeneous in IgG subclass and domain specificities; b) the genetic background influences RF specificity characteristics that may relate to pathogenicity; and c) considering the complexity of the J558 V(H) gene family and reported RF heavy chain assignments to additional V(H) gene families, it appears that V(H) genes encoding RF are diverse.

Original languageEnglish (US)
Pages (from-to)1080-1087
Number of pages8
JournalJournal of Immunology
Volume139
Issue number4
StatePublished - Oct 29 1987

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Aguado, M. T., Balderas, R. S., Rubin, R. L., Duchosal, M. A., Kofler, R., Birshtein, B. K., Secher, D. S., Dixon, F. J., & Theofilopoulos, A. N. (1987). Specificity and molecular characteristics of monoclonal IgM rheumatoid factors from arthritic and non-arthritic mice. Journal of Immunology, 139(4), 1080-1087.