Regulated apoptosis is essential for both the development and the subsequent maintenance of the immune system. Interleukins, including IL-2, IL-4, IL-7 and IL-15, heavily influence lymphocyte survival during the vulnerable stages of VDJ rearrangement and later in ensuring cellular homeostasis, but the genes specifically responsible for the development and maintenance of lymphocytes have not been identified. The Anti apoptotic protein Mcl-1 (myeloid cell leukemia sequence 1 (BCL2-related)) is an attractive candidate, as it is highly regulated, appears to enhance short-term survival and functions at an apical step in genotoxic deaths. However, Mcl-1 deficiency results in peri-implantation lethality. Mice, conditional for Mcl-1, display a profound reduction in B and T lymphocytes when Mcl-1 is removed. Deletion of Mcl-1 during early lymphocyte differentiation increases apoptosis and arrests the development at pro-B-cell and double negative T-cell stages. Induced deletion of Mcl-1 in peripheral B- and T-cell populations results in their rapid loss. Moreover, IL-7 both induces and requires Mcl-1 to mediate lymphocyte survival. Mcl-1 is essential both early in lymphoid development and later on in the maintenance of mature lymphocytes.
This affinity purified antibody was purified from whole rabbit serum prepared by repeated immunizations with a synthetic peptide corresponding to an internal region of mouse Mcl-1 conjugated to Keyhole Limpet Hemocyanin (KLH).