Central role for marginal zone B cells in an animal model of Sjogren's syndrome

•This manuscript shows for the first time the critical requirement of marginal zone B cells for the development of Sjogren's syndrome in IL-14 transgenic mice.•MZB are critical for development of Sjogren's syndrome in IL14aTG mice.•MZB produce lymphotoxin that is involved in the pathophysiology of Sjogren's syndrome.

Patients with Sjogren's syndrome (SS) have been shown to have abnormal B cell function and increased numbers of marginal zone B cells (MZB and MZB precursors. The current studies utilized the Interleukin 14 alpha transgenic mouse model (IL14aTG) for SS to investigate the roles of marginal zone B cells (MZB) of the innate immune system in the pathophysiology of the disease. Eliminating MZB from IL14aTG mice by B cell specific deletion of RBP-J resulted in complete elimination of all disease manifestations of SS. Mice had normal salivary gland secretions, negative autoantibodies and normal histology of the salivary and lacrimal glands compared to IL14aTG mice at the same time points. In contrast, eliminating B1 cells by deleting btk did not ameliorate the disease. Therefore, MZB are critical for the development of SS.