Deletion of CTLA-4 in B-1a cells led to higher production of autoantibodies, increased the number of Tfh cells and germinal centers, and promoted cell differentiation into APCs and greater self-replenishment in the mice, which caused disruption of immune homeostasis, loss of immune tolerance, and the development of autoimmune disease in the late life of the mice (87). Here, CTLA4 is linked to autoimmune disease.