B cell phenotypes, signaling and their roles in secretion of antibodies in systemic lupus erythematosus.

B cells play a pivotal role in the initiation and perpetuation of SLE. Because SLE is molecularly and clinically heterogeneous, efficacious targeted therapy to clinical remission has not yet been established in SLE. We have found i) statistical clustering between Tfh cells and class-switched memory B cells and the upregulated transition from CXCR5 IgM memory B cells to CXCR3 class-switched memory B cells in SLE by 8-color flow cytometry, ii) the involvement of Syk, Btk and JAK in the activation and differentiation of B cells in SLE, iii) SLE patients was divided to 3 groups based on immunophenotypic analysis and statistical analysis and patients in the Tfh/class-switched B cell-dominant group were most refractory to conventional therapies although 3 groups had similar clinical features. Thus, novel therapies targeting Tfh-memory B cell interaction are anticipated in certain subpopulation of SLE patients, which leads to the precision medicine in SLE.