The Lyn-mediated phosphorylation of ITIM-containing negative receptors and subsequent activation of the inhibitory phosphatases, SHP-1 and SHIP-1, that leads to the down-regulation of BCR-mediated signaling cascades and inhibition of SFK activity represents a critical component in B cell signaling that prevents the development of autoimmunity. The gene discussed is INPP5D; the disease is Autoimmunity.