B. independent of AID expression, as GC B cells from AID -/- mice retained heightened expression of SHR proteins. In consideration of the critical role that CD4+ T cells play in inducing the SHR process, our data suggest a novel role for CD4+ T cells in the tumor suppression of GC/post-GC B cells. Introduction Among all types of hematologic malignancies, more than 75% of patients in the United States are classified as having non-Hodgkin’s lymphomas, Hodgkin’s disease, chronic lymphocytic Ombitasvir (ABT-267) leukemia, or multiple myeloma [1], [2]. Of note, each of these derive from germinal center (GC) or post-GC B cells, thereby raising the important question of what makes mature B cells so uniquely predisposed to malignant transformation. The likely answer is that the GC reaction itself renders B cells highly susceptible to acquisition of non-immunoglobulin mutations and genomic instabilities [3], [4], [5], [6], [7], and therefore functions as the bottleneck of the genetic wellness of B lineage cells. Consistent with this notion, various cytogenetic abnormalities are notoriously associated with this group of malignancies. However, it remains unclear how the mutations and/or genomic instabilities that are the inevitable by-product of the genome-altering process of somatic hypermutation are suppressed during normal GC reactions, and how this tumor suppression Col13a1 mechanism fails in B lineage malignancies. To better understand these questions, it is essential to study in greater depth the mechanisms governing DNA repair in GC B cells. In all somatic cells, there is a delicate balance between ongoing levels of DNA damage and repair activity mediated by constitutively expressed DNA repair proteins. The consequences of upsetting this balance by increasing the level of DNA damage or by mutational inactivation of DNA repair genes are highly deleterious and result in the development of cancers in humans and in mouse models [8], [9], [10], [11]. Furthermore, many human sporadic cancers also possess hallmarks of DNA repair deficiencies such as cytogenetic abnormalities, microsatellite instability (MSI), and resistance to DNA damaging therapies [12]. GC Ombitasvir (ABT-267) B cells have an added burden to contend with, i.e., collateral DNA damage induced by the highly mutagenic enzyme, AID. AID is necessary for the physiological somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin (Ig) genes, and it is now known that AID also causes pathogenic off-target mutations to many other genomic loci [5], [13] and results in tumor development [14], [15], [16] and progression [17]. The additional burden of AID’s mutagenic Ombitasvir (ABT-267) activity raises the tantalizing possibility that B lineage cells require significant additional repair capacity supplementary to constitutively expressed DNA repair factors in order to maintain the tumor suppression balance. We hypothesize that such additional DNA repair capacity results from the temporal induction of expression of various DNA repair genes specifically in GC B cells, and we term this putative tumor suppressive DNA repair mechanism somatic hyperrepair (SHR). In this study, we demonstrate the existence, composition, and function of SHR in GC B cells and discuss its possible role in the development of certain hematologic malignancies. Materials and Methods Ethics statement Mayo Clinic Institutional Review Board approval was obtained for use of human blood and tonsil tissue. Informed consent was not required as this material is considered by the Institutional Review Board as waste material generated during either blood donation or surgery. In addition, patient samples.