Follicular B cells, not Marginal zone B cells, preferentially contribute to development of spontaneous autoimmune thyroiditis (SAT) and are targets of anti-CD20 therapy (56.12)

Abstract

Abstract SAT in NOD.H-2h4 mice is a chronic organ-specific autoimmune disease characterized by mononuclear cell infiltration of the thyroid and destruction of thyroid follicles by infiltrating inflammatory cells. Like other autoimmune diseases, B cells play a critical role in pathogenesis of SAT as important antigen presenting cells (APCs) for activation of CD4+ T cells. However it is not yet known which subsets of B cells are important for SAT development. In this study, we found that expression of the co-stimulatory molecules CD80 and CD86 was significantly increased on splenic CD23hiCD21low follicular (FO) B cells, but not marginal zone (MZ) B cells, after SAT development, but absolute numbers and percentages of splenic FO B cells were not altered. In draining lymph nodes, CD40 expression on FO B cells was also increased in mice with SAT. All thyroid infiltrating B cells in mice with SAT were FO B cells. Depletion of FO B cells by anti-CD20 antibody ameliorated established SAT, and anti-thyroglobulin antibody levels were reduced. Moreover, administering anti-CD20 to mice with established SAT results in depletion of B cells in the thyroid and depletion of thyroid B cells is longer lasting than depletion of splenic B cells. On the basis of these findings, we suggest the FO subset of B cells preferentially contributes to SAT development and persistence, and targeting FO B cells after disease develops provides an effective means to treat autoimmune diseases.