The Role of B Cells in RA
The 3 important roles B cells may play in RA & the mechanism of action of Rituxan
RITUXAN is the first and only RA therapy that selectively targets CD20+ B Cells1
For much of the past 20 years, RA has mainly been considered a T-cell–mediated disease.2 Recently, however, new evidence has led to strong interest in B cells and their important roles in the pathogenesis of RA.3
Watch Video
Roles of B Cells in RA and the MOA of RITUXAN
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This video depicts:
- An introduction to selective targeting of CD20+ B cells in RA
- The 3 important roles B cells may play in the pathogenesis of RA
- How RITUXAN works in RA
The 3 potential roles of B cells in rheumatoid arthritis
View a diagram depicting The 3 Potential Roles of B Cells in Rheumatoid Arthritis
View Diagram
Antigen Presentation
Autoantibody Production
Cytokine Production
B cells are believed to play 3 important roles in RA: antigen presentation
* MHC = Major histocompatibility complex. TCR = T-cell receptor.
As highly efficient antigen-presenting cells, B cells may contribute significantly to T-cell responses in RA.3-9
In certain circumstances B cells may be up to 10,000-fold more efficient than other APCs.4-6
- B cells may provide both signals needed to activate T cells3,4,8
- B cells have been shown to play an important role in T-cell activation in the synovium from animal models.3,4
- Activated T cells produce proinflammatory cytokines such as TNF-α and IL-1 that directly and indirectly perpetuate inflammation.7
- RF-producing, autoreactive B cells possess a specialized ability to bind any antigen that is already part of an antibody immune complex.9,10
- RF-producing, autoreactive B cells may present a variety of antigens to antigen-specific T cells.9
This can lead to even greater cytokine production and resulting inflammation.
B cells are believed to play 3 important roles in RA: autoantibody production
Autoreactive B cells produce autoantibodies that may help drive the disease process in RA.2,3,5,10,11,15
B cells produce autoantibodies such as RF,* anti-CCP,† anti-GPI,‡ and anti-RA33.§ RF immune complexes formed within the synovium may:
- Activate the complement system and stimulate an immune response3,10
- Bind to and activate macrophages in the synovium11
Macrophages activated by immune complexes produce proinflammatory cytokines that perpetuate inflammation.11
*Rheumatoid factor (RF): antibody against IgG.3
† Anti-CCP: antibody against citrullinated proteins.3
‡ Anti-GPI: antibody against glucose-6-phosphate isomerase enzyme.2,3
§ Anti-RA33: antibody against RA33, an RNA-binding protein involved in regulating gene expression.15
B cells are believed to play 3 important roles in RA: antigen production
Activated B cells may produce cytokines known to promote inflammation in RA.3,4,12,13 B cells may be activated to produce cytokines such as TNF-α, IL-6, IFN-γ, and lymphotoxin in a variety of ways:
- Antigen binding to the B-cell receptor (BCR)4,12
- Binding of the costimulatory ligand found on activated T cells, macrophages, and dendritic cells to the costimulatory receptor on B cells4,12,13
- Exposure of B cells to cytokines produced by other immune cells4
B-cell–produced lymphotoxin may also indirectly perpetuate RA by promoting the formation of new lymphoid structures in the synovium4:
- The chronically inflamed synovium of patients with RA contains abnormally large numbers of immune-cell infiltrates, including B cells, T cells and macrophages.7
- The organization of these cells into lymphoid structures may help perpetuate the autoimmune reaction and joint inflammation3,4,7,16
