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Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
Published on: June 8, 2022
Reduced receptor editing in lupus-prone MRL/lpr mice
Jennifer L Lamoureux1, Lisa C Watson, Marie Cherrier
1Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
The Journal of Experimental Medicine
|October 31, 2007
Summary
In lupus-prone mice, the B cell receptor editing process in bone marrow is less efficient. This defect allows self-reactive B cells to escape, potentially contributing to the development of autoimmunity.
Area of Science:
- Immunology
- Autoimmunity
- B cell biology
Background:
- The B cell repertoire initially contains self-reactive specificities.
- B cell tolerance checkpoints eliminate self-reactivity, primarily through receptor editing in immature B cells.
- A second checkpoint exists in transitional B cells in the spleen, which is known to be defective in lupus.
Purpose of the Study:
- To investigate potential breakdowns in central B cell tolerance within the bone marrow of lupus-prone mice.
- To determine if receptor editing efficiency is impaired in the bone marrow of the MRL/lpr lupus-prone strain.
Main Methods:
- Utilized an in vitro system to stimulate bone marrow immature B cells with receptor-editing signals (anti-idiotype antibody or self-antigen).
- Compared receptor editing efficiency in MRL/lpr 3-83 transgenic immature B cells versus B10 transgenic cells.
- Quantified endogenous rearrangement, recombination activating gene (RAG) mRNA upregulation, and CD19/immunoglobulin M (IgM) downregulation.
Main Results:
- MRL/lpr transgenic immature B cells exhibited less endogenous rearrangement and lower upregulation of RAG mRNA compared to B10 cells.
- CD19 and IgM downregulation, indicative of receptor editing, was fivefold less pronounced in MRL/lpr mice.
- These findings suggest a defect in the receptor editing mechanism within the bone marrow of lupus-prone mice.
Conclusions:
- Receptor editing is less efficient in the bone marrow of lupus-prone MRL/lpr mice.
- This impaired central tolerance mechanism may permit autoreactive B cells to escape the bone marrow.
- Reduced receptor editing efficiency could predispose MRL/lpr mice to autoimmunity.
