Subset size, activation threshold and distribution of autoreactive MZ and FO B cells do not differ in a sex-specific manner in the NZB/W F1 murine lupus model: An experimental mouse study

Objectives: Systemic lupus erythematosus (SLE) shows a strong sex bias, preferentially affecting females, and B cells are thought to play a pivotal role in its pathogenesis. Here, we compared the splenic B-cell compartments, their autoreactivity and activation threshold of female and male NZB/W F1, a murine lupus model reflecting the sex bias observed in patients with SLE. Methods: Autoantibody levels and the amount of autoantibody secreting cells were determined using ELISA and ELISPOT. Flow cytometry and immunofluorescence were applied to analyse the composition of the splenic B-cell pool. Purified follicular (FO) and marginal zone (MZ) B cells were stimulated and the frequency of autoreactive cells was determined. Finally, the proliferative response of FO and MZ B cells upon stimulation was assessed using CFSE dilution and [3H]-Thymidin incorporation. Results: Higher autoantibody titres were detected in female NZB/W F1 mice, which were mainly produced in the spleen. Analysing the composition of the splenic B-cell subsets, no differences were found prior to disease development. Autoreactive dsDNA-specific B cells were mostly found in the MZ compartment, while SmD1(83-119)-reactive cells were more evenly distributed. Equal frequencies of autoreactive B cells were found in female and malemice, and no difference in the response to polyclonal stimuli of the cells of both sexes was detected. Conclusions: No differences in the composition or functionality of splenic B cells were observed that account for the different disease course in both sexes.