BTK and isolated agammaglobulinemia: In the absence of mammalian Btk, B-cell receptor signaling is insufficient for the generation of mature B-lymphocytes [5], [6], [7], resulting in the immunodeficiency disease X-linked agammaglobulinemia (XLA) in humans [8], [9] and X-linked immunodeficiency disease (Xid) in mice [10], [11].