Innate immunity and human B cell clonal expansion: effects on the recirculating B2 subpopulation
Patricia K A Mongini1, John K Inman, Hanna Han
1Department of Rheumatology, Hospital for Joint Diseases, New York University Medical Center, NY 10003, USA. patricia.mongini@med.nyu.edu
Journal of Immunology (Baltimore, Md. : 1950)
|October 21, 2005
Summary
In inflammation, B cell-activating factor (BAFF) and IL-4 synergize with B cell receptor (BCR) signaling to drive clonal expansion of B2 cells, potentially promoting autoimmunity.
Area of Science:
- Immunology
- Autoimmunity
- Cell Biology
Background:
- Ectopic lymphoid tissues in nonlymphoid tissues are linked to autoimmune diseases.
- Understanding the formation of these tissues is crucial for autoimmune disease research.
Purpose of the Study:
- To investigate the cooperative roles of innate immune molecules in T cell-independent B cell expansion.
- To determine if B cell-tropic molecules can foster clonal expansion of human B2 cells with limited B cell receptor (BCR) engagement.
Main Methods:
- Studied synergy between BCR coligation with CD21/CD19, B cell-activating factor (BAFF), and IL-4.
- Analyzed effects on mature human B2 cell clonal expansion and expression of CD86 and DR.
- Investigated mechanisms including cell cycle progression, receptor regulation, apoptosis, and antiapoptotic protein expression.
Main Results:
- Significant synergy observed between BCR coligation, BAFF, and IL-4 in B cell expansion and sustained CD86/DR expression.
- Cooperative effects promoted cell cycle progression and viability.
- IL-4 regulated BAFF receptor increases induced by BCR:CD21 coligation.
- BAFF and IL-4 reciprocally reduced apoptosis, with BAFF sustaining Mcl-1 expression.
Conclusions:
- Limited BCR engagement with C3dg-coated antigens in an inflammatory milieu with BAFF and IL-4 can drive significant B2 cell clonal proliferation.
- Expansion of rare autoantigen-presenting B cells through this mechanism may promote both B cell and T cell autoimmunity.
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