Abstract
B cells play a pivotal role in the pathogenesis of autoimmune diseases. In addition, B cells require interaction with helper CD4+ T cells to become activated. We assessed change of gene regulatory network that controls B cell differentiation after stimulation with BCR cross-linking, sCD40L, Toll-like Receptor (TLR) and cytokines such as IL-4/IL-21 in vitro. We found that combination with BCR, CD40 and TLR9 or IL-4/IL-21 signal via tyrosine kinases such as Syk/Btk/JAK caused robust gene expression of AICDA, BCL6, XBP1 and IgG production. We found that levels of Syk/Btk phosphorylation in B cells were preferentially higher in RA and SLE patients compared to healthy subjects. RA patients with higher p-Syk levels were significantly correlated to strongly positive for anti-citrullinated protein antibodies (ACPAs). Treatment with abatacept significantly reduced the levels of p-Syk in RA peripheral blood B cells, and also reduced the proportion of follicular helper T (Tfh) cells. We highlight tyrosine kinase such as Syk/Btk/JAK as potential targets for inhibiting B cell-T cell interactions in autoimmune diseases such as RA and SLE. We also state recent evidence of these drugs.
