Philip D. Bardwell

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Affinity maturation of the humoral immune response is caused by single base changes that are introduced into the V regions of the Ig genes during a brief period of B cell differentiation. It has recently become possible to study V region mutation in some human Burkitt's lymphoma cell lines that mutate their V regions and express surface markers that suggest(More)
The Bcl-2 family of proteins plays a critical role in controlling immune responses by regulating the expansion and contraction of activated lymphocyte clones by apoptosis. ABT-737, which was originally developed for oncology, is a potent inhibitor of Bcl-2, Bcl-x(L), and Bcl-w protein function. There is evidence that Bcl-2-associated dysregulation of(More)
Somatic hypermutation and class switch recombination (CSR) contribute to the somatic diversification of antibodies. It has been shown that MutS homologue (Msh)6 (in conjunction with Msh2) but not Msh3 is involved in generating A/T base substitutions in somatic hypermutation. However, their roles in CSR have not yet been reported. Here we show that(More)
The generation of protective antibodies requires somatic hypermutation (SHM) and class-switch recombination (CSR) of immunoglobulin genes. Here we show that mice mutant for exonuclease 1 (Exo1), which participates in DNA mismatch repair (MMR), have decreased CSR and changes in the characteristics of SHM similar to those previously observed in mice mutant(More)
The production of high-affinity protective antibodies requires somatic hypermutation (SHM) of the antibody variable (V)-region genes. SHM is characterized by a high frequency of point mutations that occur only during the centroblast stage of B-cell differentiation. Activation-induced cytidine deaminase (AID), which is expressed specifically in(More)
Repulsive guidance molecule A (RGMa) is a potent inhibitor of neuronal regeneration and a regulator of cell death, and it plays a role in multiple sclerosis (MS). In autopsy material from progressive MS patients, RGMa was found in active and chronic lesions, as well as in normal-appearing gray and white matter, and was expressed by cellular meningeal(More)
Apoptosis controls the adaptive immune system through regulation of central and peripheral lymphocyte deletion. Therefore, substances that selectively interact with the intrinsic apoptosis pathway in lymphocytes offer unexplored opportunities to pharmacologically modulate the immune response. Here, we present evidence that the BH3-mimetic ABT-737 suppresses(More)
Induction of mixed hematopoietic chimerism results in donor-specific immunological tolerance by apoptosismediated deletion of donor-reactive lymphocytes. A broad clinical application of this approach is currently hampered by limited predictability and toxicity of the available conditioning protocols. We developed a new therapeutic approach to induce mixed(More)
BACKGROUND Studies of bone marrow transplantation (BMT) from wild-type mice or rats to alpha1,3-galactosyltransferase (GalT) knockout mice have demonstrated that induction of mixed chimerism tolerizes not only T cells, but also natural antibody-producing B cells, even across xenogeneic barriers. Given that rodent cells express lower levels of the alphaGal(More)