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Early preplasma cells define a tolerance checkpoint for autoreactive B cells
Donna A Culton1, Brian P O'Conner, Kara L Conway
1Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|January 6, 2006
Summary
Researchers identified a new B cell tolerance checkpoint regulating autoreactive cells before they become antibody-secreting plasma cells (PCs). This checkpoint prevents autoimmunity but is bypassed in MRL/lpr mice.
Area of Science:
- Immunology
- Autoimmunity
- Cell Biology
Background:
- Antibody-secreting plasma cells (PCs) are crucial for humoral immunity.
- Autoreactive B cells pose a risk for autoimmune diseases.
- Regulation of B cells is essential for maintaining self-tolerance.
Purpose of the Study:
- To investigate the regulation of autoreactive B cells specific for the Smith (Sm) ribonucleoprotein at an early pre-plasma cell (pre-PC) stage.
- To identify a novel B cell tolerance checkpoint.
- To understand how this checkpoint is overcome in autoimmune conditions.
Main Methods:
- Phenotypic characterization of pre-PCs using markers like CD138, CD19, and B220.
- Analysis of antigen (Ag) dependence and cellular localization of anti-Sm pre-PCs.
- Assessment of cell turnover, cell death rates, and transcriptional regulation (B lymphocyte-induced maturation protein-1).
- Comparison between normal mice and autoimmune MRL/lpr mice, including B lymphocyte stimulator receptor profiling.
Main Results:
- A high frequency of autoreactive pre-PCs specific for Sm was found in normal mice, located near T cell-B cell borders.
- These anti-Sm pre-PCs exhibited characteristics of PC differentiation but did not secrete antibodies, indicating regulation.
- Anti-Sm pre-PCs showed increased turnover and cell death compared to non-Sm-specific pre-PCs.
- Regulation occurred upstream of B lymphocyte-induced maturation protein-1, and this checkpoint was bypassed in MRL/lpr mice with altered B lymphocyte stimulator receptor expression.
Conclusions:
- A novel B cell tolerance checkpoint regulates autoreactive pre-PCs before terminal differentiation into antibody-secreting plasma cells.
- This checkpoint is critical for preventing autoimmunity by controlling autoreactive B cells.
- Dysregulation or bypass of this checkpoint, potentially linked to altered B lymphocyte stimulator receptor signaling, contributes to autoimmunity in MRL/lpr mice.