Immunodeficiency can occur through abberant signaling of the pre-B receptor
•Btk: Bruton’s tyrosine kinase. Mutation causes a profound B-lineage specific immune deficiency (Bruton’s X-linked agammaglobulinemia, XLA) in which no mature B-cells are produced.  •Mouse equivalent (xid) more “leaky”; some mature B cells get by pre-B block, but they are signaling compromised as well. •Tec family tryrosine kinase regulated via PKC, Ca2+ pathway (Chapter 6);
•Mutations in plextrin homology domain (PHD)