Positive Selection of Natural Autoreactive B Cells

TLDR

Self‑antigens shape lymphocyte development, with T cells undergoing both positive and negative selection, while the role of self‑antigen in positively selecting B cells has been unclear. A mouse model with germ‑line encoded Thy‑1 specificity was used to show that self‑antigen drives accumulation of autoreactive B cells and induces serum autoantibody production. The study demonstrates that autoreactive B cells undergo positive selection and are maintained by their self‑reactivity.

Abstract

Lymphocyte development is critically influenced by self-antigens. T cells are subject to both positive and negative selection, depending on their degree of self-reactivity. Although B cells are subject to negative selection, it has been difficult to test whether self-antigen plays any positive role in B cell development. A murine model system of naturally generated autoreactive B cells with a germ line gene–encoded specificity for the Thy-1 (CD90) glycoprotein was developed, in which the presence of self-antigen promotes B cell accumulation and serum autoantibody secretion. Thus, B cells can be subject to positive selection, generated, and maintained on the basis of their autoreactivity.