Background Despite growing insights in the breach of immune tolerance, it remains currently unknown which molecules drive or control pathogenic B cells in human rheumatoid arthritis (RA). Recently we have identified a marked increase in expression of the B cell-specific transcriptional co-activator Bob1 in RA synovitis. Additionally, we found that mice lacking Bob1 failed to produce pathogenic anti-collagen autoantibodies and were completely protected from collagen-induced arthritis (CIA), the animal model of RA.
Objectives We aimed to determine whether this remarkable resistance to CIA in the absence of Bob1 is caused due to lack of functional germinal centers or by intrinsic defects in the B cells of these animals. Furthermore we proceeded to prove that the resistance to CIA is caused exclusively by B cells lacking Bob1.
Methods First, to determine whether intrinsic B cell defects were the basis of the CIA resistance, we transferred wild type (WT) B cells to Bob1-deficient mice, lacking functional germinal centers (GC), followed by CIA.
Then, in order to prove that functional Bob1 exclusively in B cells is required for susceptibility to CIA, we adoptively transferred various combinations of WT and Bob1-deficient B and T cells to RAG-1-null mice followed by CIA induction.
Results After transfer of WT cells to Bob1-deficient animals, Bob1-deficient mice were still resistant to CIA, suggesting that resistance to CIA is related to GC formation rather to intrinsic B cells defects in the absence of Bob1 and that GCs are important in the pathogenesis of CIA.
In the RAG-1-null adoptive transfer model we only observed clinical symptoms of arthritis in the mice that received WT B cells. Moreover, anti-collagen antibodies were only found in the serum of mice that had received WT B cells. Mice lacking Bob1 in their transferred B cells were still protected from CIA.
Conclusions This data strongly suggest that expression of Bob1 in B cells is indispensable for GC formation and required for the development of CIA and the formation of anti-collagen antibodies. The mechanisms behind an aberrant Bob1 expression and the break of peripheral tolerance in RA is currently under investigation.
Disclosure of Interest None declared