title: [The importance of B cell-T cell interaction in autoimmune diseases].
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.
authors.affiliation: The First Department of Internal Medicine, University of Occupational and Environmental Health.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Iwata
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000627:therapeutic use; D053612:Janus Kinases / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000627:therapeutic use; D000072377:Syk Kinase; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases; D053612:Janus Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase