Physicochemical characteristics of human IgG Fc fragments that expose regulatory rheumatoid factor neoepitopes and may show promise as antirheumatic agents

2020 ◽  
Vol 67 (2) ◽  
pp. 287-293 ◽  
Author(s):  
Alexandr Sidorov ◽  
Liubov Beduleva ◽  
Igor Menshikov ◽  
Alexey Terentiev ◽  
Igor Cherepanov
Keyword(s):  
Rheumatoid Factor ◽  
Physicochemical Characteristics ◽  
Antirheumatic Agents ◽  
Human Igg

scholarly journals Estimation of the relative avidity of 19S IgM rheumatoid factor secreted by rheumatoid synovial cells for human IgG subclasses

1986 ◽  
Vol 29 (6) ◽  
pp. 722-729 ◽  
Author(s):  
Dick L. Robbins ◽  
Jeffrey Skilling ◽  
William F. Benisek ◽  
Richard Wistar
Keyword(s):  
Rheumatoid Factor ◽  
Igg Subclasses ◽  
Synovial Cells ◽  
Human Igg ◽  
Igm Rheumatoid Factor

scholarly journals Human immunoglobulin (IgG) induced deletion of IgM rheumatoid factor B cells in transgenic mice.

1995 ◽  
Vol 181 (2) ◽  
pp. 599-606 ◽  
Author(s):  
H Tighe ◽  
P Heaphy ◽  
S Baird ◽  
W O Weigle ◽  
D A Carson
Keyword(s):  
B Cells ◽  
Transgenic Mice ◽  
B Cell ◽  
Rheumatoid Factor ◽  
Immunoglobulin Gene ◽  
Protein Antigens ◽  
Human Igg ◽  
Variable Regions ◽  
Igm Rheumatoid Factor ◽  
Induction Of Tolerance

The singular ability of immunoglobulin genes to hypermutate their variable regions, while permitting the generation of high-affinity antibodies against foreign antigens, poses a problem in terms of maintenance of immunological self-tolerance. Immunoglobulin gene hypermutation driven by a foreign antigen has the potential to generate antibodies that cross-react with self-components. Consequently, there must exist a mechanism in the periphery for inactivation of mature autoreactive B cell clones. The classical experimental system used to address this problem is the induction of tolerance to soluble, deaggregated human IgG. We have analyzed the mechanism of induction of tolerance to human IgG using transgenic mice that express a human IgM rheumatoid factor (IgM RF) on a large proportion of their B cells. Injection of deaggregated human IgG caused a specific deletion of those B cells that express an intact IgM RF on their cell surface. The degree of RF B cell deletion was proportional to the reduction in the proliferative response of splenocytes to antigen (aggregated human IgG), or to F(ab')2 fragments of anti-human IgM antibodies. Control experiments showed that IgG administration had little effect on the numbers of mouse Ig-bearing cells or their ability to proliferate to a nonspecific mitogen. Thus, the effects of IgG on the human IgM RF B cell are antigen specific and are not due to nonspecific toxic effects of the human IgG preparation. These experiments demonstrate that peripheral exposure to IgG induces deletion of reactive B cells, without any evidence for anergy, and differ from data obtained by other investigators studying tolerance to soluble protein antigens. The results imply that human Igs have distinct properties as soluble antigens, and that peripheral nonresponsiveness to IgG may be due to lymphocyte deletion.

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