B cell receptor signaling and autoimmunity

The immune receptors of lymphocytes are able to sense the nature of bound l igands. Through coupled signaling pathways the generated signals are approp riately delivered to the intracellular machinery, allowing specific functio nal responses. A central issue in contemporary immunology is how the fate o f B lymphocytes is determined at the successive developmental stages and ho w the B cell receptor distinguishes between signals that induce immune resp onse or tolerance. Experiments with mice expressing transgenes or lacking s ignal transduction molecules that lead to abnormal lymphocyte development a nd/or response are providing important clues to the mechanisms that regulat e signaling thresholds at different developmental stages. The studies are a lso revealing novel potential mechanisms of induction of autoimmunity, whic h may have a bearing on the understanding of human diseases.