Manuscript

The maintenance of B cell tolerance is dependent on cell surface molecules that serve to modulate signaling through the B cell receptor (BCR), such as Fc gamma receptor IIb (FcγRIIb; CD32b) and complement receptor (CR) 1 (CD35) and 2 (CD21). Consequently, deficiency in these receptors might lead to autoimmunity. We have studied the basal expression of FcγRIIb, CR1 and CR2 on B cells in healthy male and female blood donors in comparison to rheumatoid arthritis (RA) patients to reveal any possible differences. Firstly, we found a gender associated difference in FcγRIIb expression, as healthy women had lower basal expression of FcγRIIb on B cells than men and the expression significantly decreased with age. Secondly, RA patients displayed lower numbers of FcγRIIb, CR1 and CR2 positive B cells and decreased FcγRIIb, CR1 and CR2 receptor expression compared to healthy controls. Furthermore, the proliferation capacity of RA B cells following low dose IgG anti-µ stimulus was investigated. Even though RA B cells had lower FcγRIIb expression, the receptor was still able to inhibit BCR-mediated proliferation, however, not as significantly as in B cells from healthy subjects. Notably, the RA B cells proliferated more frequently from a BCR-independent IL-2 stimulation than B cells from healthy controls, suggesting that IL-2 signals generated from any activated T cell may initiate an unspecific B cell proliferation in RA patients. In conclusion, the uncontrolled B cell response seen in RA patients may be associated with lower levels of inhibitory FcγRIIb, CR1 and CR2. The lower basal expression of FcγRIIb in females might contribute to the increased incidence of RA in women