Regulation of B-lymphocyte negative and positive selection by tyrosine phosphatase CD45

A cross between tyrosine phosphatase CD45-deficient mice and mice carrying immunoglobulin transgenes specific for hen egg lysozyme (HEL) shows that CD45 positively regulates antigen-receptor signaling. CD45-deficient HEL-specific B cells show diminished signaling in response to HEL. Circulating HEL autoantigen controls negative selection of mature CD45(super +/+) HEL-binding B cells. The autoantigen positively selects CD45(super -/-) HEL-binding B cells. Inherited susceptibility to autoimmune disease is possible due to changes in antigen receptor signaling.