Significance of RGS13 expression in lupus B cells.

Abstract

B cells play important roles in systemic lupus erythematosus (SLE) pathogenesis. In this study, we explored the proteins preferentially expressed in SLE B cells, especially double-negative 2 B (DN2B) and age-associated B cells (ABCs), and analysed their functions. We used our previously reported dataset to identify the mRNAs preferentially expressed in SLE B cells and confirmed their expression in each B cell subset via flow cytometry. Additionally, we also used knockout mice of the identified gene to investigate its roles. Of the 525 mRNAs exclusively upregulated in SLE B cells, regulator of G protein signalling (RGS)-13 was identified as a top-ten gene of interest. Its expression levels were determined via quantitative polymerase chain reaction and correlated with the anti-dsDNA antibody levels. Flow cytometry revealed that RGS13 levels were particularly high in DN2B cells. Among the DN2B cell differentiation-inducing factors, B cell receptor stimulation induced RGS13 expression. Total B cell, follicular B cell, and ABC numbers were reduced in the spleen, whereas the number of germinal centre B cells, which also highly express Rgs13, was unaffected in Rgs13-/- mice. Moreover, total B cell number increased in the bone marrow but remained unchanged in the peripheral blood in Rgs13-/- mice. No difference in responsiveness to ABC-inducing stimuli was observed between the Rgs13-/- and wild-type mice. Overall, RGS13 was highly expressed in lupus DN2B cells and mouse ABCs, induced by B cell receptor stimulation, and indirectly associated with the differentiation and maintenance of ABCs relevant to autoimmunity.