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Defective Fc gamma RII gene expression in macrophages of NOD mice: genetic linkage with up-regulation of IgG1 and IgG2b in serum.

J J Luan, R C Monteiro, C Sautès, G Fluteau, L Eloy, W H Fridman, J F Bach and H J Garchon
J Immunol November 15, 1996, 157 (10) 4707-4716;
J J Luan
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R C Monteiro
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C Sautès
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G Fluteau
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L Eloy
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W H Fridman
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J F Bach
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H J Garchon
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Abstract

A quantitative trait locus for increased IgG serum levels in the NOD mouse strain was mapped to distal chromosome 1, close to the fcgr2 locus encoding the low-affinity type II receptor for the Fc portion of IgG (Fc gamma RII). Expression of membrane-inserted (b2) and soluble (b3) isoforms of Fc gamma RII was strongly decreased in macrophages of NOD compared with C57BL/6 (B6) mice. In contrast, B cell-specific (Fc gamma RIIb1) isoform was only slightly decreased and Fc gamma RIII was not altered. This Fc gamma RII regulatory defect was cis-encoded by fcgr2 or by a closely linked locus, occurred at the mRNA level, and was associated with multiple mutations in the fcgr2 gene promoter. In relation with this defect, binding of IgG1- and IgG2b- but not IgG2a-opsonized RBC by macrophages of NOD and congenic B6.NOD-fcgr2 mice was severely impaired, but was normal in macrophages of NOD.B6-fcgr2 congenic mice, indicating that Fc gamma RII plays a nondispensable role in binding of IgG1 and IgG2b isotypes. Likewise, serum levels of IgG1 and IgG2b but not IgG2a were up-regulated in NOD compared with NOD.B6-fcgr2 congenic mice. These findings indicate that macrophage Fc gamma RII may regulate serum IgG1 and IgG2b through their catabolism, and validate the NOD strain as a model to investigate the functions of Fc gamma RII isoforms.

  • Copyright © 1996 by American Association of Immunologists

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The Journal of Immunology
Vol. 157, Issue 10
15 Nov 1996
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Defective Fc gamma RII gene expression in macrophages of NOD mice: genetic linkage with up-regulation of IgG1 and IgG2b in serum.
J J Luan, R C Monteiro, C Sautès, G Fluteau, L Eloy, W H Fridman, J F Bach, H J Garchon
The Journal of Immunology November 15, 1996, 157 (10) 4707-4716;

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Defective Fc gamma RII gene expression in macrophages of NOD mice: genetic linkage with up-regulation of IgG1 and IgG2b in serum.
J J Luan, R C Monteiro, C Sautès, G Fluteau, L Eloy, W H Fridman, J F Bach, H J Garchon
The Journal of Immunology November 15, 1996, 157 (10) 4707-4716;
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Print ISSN 0022-1767        Online ISSN 1550-6606