Secondary lymphoid organ stroma activate and elaborate regulatory T cells to suppress autoantibody production in a novel model of systemic autoimmunity

Preclinical models of lupus indicate that T cell-B cell collaboration drives pathogenic antinuclear antibody (ANA) production and sustains T cell activation. Mechanisms that normally limit T cell activation of autoreactive B cells remain incompletely resolved but potentially include the absence of autoreactive effector T cell subsets and/or the presence of autoantigen-specific regulatory T cells (Tregs). Several studies have addressed this issue by using experimental systems dependent on transgenic autoreactive B cells, but much less is known about the activation of autoreactive B cells present in a polyclonal repertoire. We have now explored the role of effector T cells and Tregs using mice that express an inducible pseudo-autoantigen on antigen presenting cells (APCs) including a normal B cell repertoire. Bone marrow chimera experiments demonstrated that radioresistant non-hematopoietic stromal APCs (rAPC) present in the thymus and in peripheral lymphoid tissue induced the differentiation and expansion of a subset of CD62L+CD69+ Tregs associated with decreased autoantibody production and MHC-II. In this study, we show that secondary lymph node stromal cells may be crucial for suppression of endogenous autoreactive B cells in the setting of robust T cell help.