Background: Rituximab, a B cell-targeting drug, is effective in some uveitis patients, suggesting that B cells play a role in uveitis. Understanding their role will help identify patients who would benefit most from rituximab. Here we analyzed both gene expression and B cell receptor (BCR) sequences to characterize ocular B cells in human uveitis.
Methods: We performed single cell RNA and VDJ sequencing on ocular and peripheral blood immune cells from 23 uveitis patients and two controls.
Results: B cells comprised 5% (range 0-43%) of aqueous immune cells in our cohort. A subset of patients had highly increased B cell numbers, comprising more than 20% of the ocular infiltrate. B cell clonal expansion was also greater in these eyes compared to blood, suggesting that local antigen-driven expansion of B cells may occur in some patients with uveitis. Ocular B cells were also enriched in gene expression consistent with B cell activation/differentiation, including FCRL4 and FCRL5, important for tertiary lymphoid organs; AICDA, a driver of somatic hypermutation; and CXCR3, which promotes differentiation to plasma cells.
Conclusion: Taken together, these results suggest that B cells are enriched in a subset of uveitis patients and may locally expand and differentiate in response to antigen. B cells may drive ocular inflammation in a subset of patients and thus, analysis of ocular B cells may help identify patients who would benefit from B cell-targeted therapies.
