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

Research output: Contribution to journalArticle

27 Citations (Scopus)

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 - 1987
Externally publishedYes

Fingerprint

Rheumatoid Factor
Immunoglobulin M
Rheumatoid Arthritis
Immunoglobulin G
Genes
Hybridomas
Clone Cells
Inbred MRL lpr Mouse
Staphylococcal Protein A
Arthritis
Virulence
RNA
Gene Expression

ASJC Scopus subject areas

  • Immunology

Cite this

Aguado, M. T., Balderas, R. S., Rubin, R. L., Duchosal, M. A., Kofler, R., Birshtein, B. K., ... 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.

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

In: Journal of Immunology, Vol. 139, No. 4, 1987, p. 1080-1087.

Research output: Contribution to journalArticle

Aguado, MT, Balderas, RS, Rubin, RL, Duchosal, MA, Kofler, R, Birshtein, BK, Secher, DS, Dixon, FJ & Theofilopoulos, AN 1987, 'Specificity and molecular characteristics of monoclonal IgM rheumatoid factors from arthritic and non-arthritic mice', Journal of Immunology, vol. 139, no. 4, pp. 1080-1087.
Aguado MT, Balderas RS, Rubin RL, Duchosal MA, Kofler R, Birshtein BK et al. Specificity and molecular characteristics of monoclonal IgM rheumatoid factors from arthritic and non-arthritic mice. Journal of Immunology. 1987;139(4):1080-1087.
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. / Specificity and molecular characteristics of monoclonal IgM rheumatoid factors from arthritic and non-arthritic mice. In: Journal of Immunology. 1987 ; Vol. 139, No. 4. pp. 1080-1087.
@article{9998d2be789b48c9a543b0a084fbd9b8,
title = "Specificity and molecular characteristics of monoclonal IgM rheumatoid factors from arthritic and non-arthritic mice",
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.",
author = "Aguado, {M. T.} and Balderas, {R. S.} and Rubin, {R. L.} and Duchosal, {M. A.} and R. Kofler and Birshtein, {B. K.} and Secher, {D. S.} and Dixon, {F. J.} and Theofilopoulos, {A. N.}",
year = "1987",
language = "English (US)",
volume = "139",
pages = "1080--1087",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "4",

}

TY - JOUR

T1 - Specificity and molecular characteristics of monoclonal IgM rheumatoid factors from arthritic and non-arthritic mice

AU - Aguado, M. T.

AU - Balderas, R. S.

AU - Rubin, R. L.

AU - Duchosal, M. A.

AU - Kofler, R.

AU - Birshtein, B. K.

AU - Secher, D. S.

AU - Dixon, F. J.

AU - Theofilopoulos, A. N.

PY - 1987

Y1 - 1987

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0023258987&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023258987&partnerID=8YFLogxK

M3 - Article

VL - 139

SP - 1080

EP - 1087

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 4

ER -