Investigating the role of MZB and B1 Cells in Sjögren’s Disease (159.22)

Abstract

Abstract We have previously demonstrated that IL14a transgenic mice (IL14aTG) reproduce features of Sjogren’s disease (SD) seen in patients in the same relative time frame, including autoantibodies, early destruction of the salivary and lachrymal glands, infiltration of the salivary and lachrymal glands with lymphocytes, lymphocytic pneumonia, mild renal disease and eventually lymphoma (J.Immunol. 177: 5676, 2006 and Clin. Immunol. 130:304, 2009). We have more recently demonstrated that lymphotoxin is an important early mediator of salivary gland injury in IL14aTG mice and patients with SD (J.Immunol. 185: 6355, 2010). In our current studies we investigate the role of MZB and B1 cells in SD in IL14aTG mice. We demonstrate that IL14aTG mice lacking MZB cells (IL14aTG.CD19Cre.RBPj-/-) do not develop any features of SD up to the ages of 18 months. However, IL14aTG mice lacking Bruton’s tyrosine kinase (btk; IL14aTG.btk-/-), and hence B1 cells, develop more severe and accelerated SD with B cell lymphomas by 10 months of age, about 3 months earlier than IL-14a TG mice. Our hypothesis is that MZB and MZB precursors (MZBP) trafficking in the salivary and lachrymal glands are critical for inducing SD. Mice lacking B1 cells via the deletion of Bruton’s tyrosine kinase (btk) have accelerated SD because of increased numbers of MZB and MZBP along with decreased numbers of regulatory B cells. Current studies are evaluating these hypotheses.