E2A, HEB and E2–2 genes encode a group of basic helix‐loop‐helix (bHLH) transcription factors that are structurally and functionally similar. Deletion of the genes encoding either of these proteins leads to early lethality and a block in B lymphocyte development. Evidence for a function in T lymphocyte development has, however, only been reported for E2A and HEB. To further elucidate the role of E2–2 at developmental stages that have proven difficult to study due to the early lethality phenotype of mice defective in E2–2, we generated and analyzed mice conditionally mutated in the E2–2 gene. These mice are mosaic with respect to E2–2 expression, consisting of cells with either one functional and one null mutated E2–2 allele or two null mutated alleles. Using this experimental model, we find that cells with a homozygous null mutated E2–2 gene are under‐represented in B lymphocyte as well as T lymphocyte cell lineages as compared to other hematopoietic or non‐hematopoietic cell lineages. Our data suggests that E2–2 deficiency leads to a partial block in both B and T lymphocyte development. The block in T cell development appears to occur at an early stage in differentiation, since skewing in the mosaicism is observed already in CD4+8+ double‐positive thymocytes.

Low-dose and low-dose-rate radiation are able to induce significant apoptosis, and apoptosis may be one of the mechanisms by which low-dose radiation causes growth inhibition.

No abstract

BACKGROUND Different strategies can be used to improve the tumor:non‐tumor ratio of radiolabeled antibodies in immunotargeting. One approach is to use secondary antibodies to clear out redundant, circulating primary antibodies. In the current study, the in vitro complex formation and in vivo clearing capabilities and metabolism of the monoclonal antibody TS1 and its monoclonal anti‐idiotype, αTS1, were studied. METHODS Complex formation studies were performed using polyacrylamide gel electrophoresis (PAGE), gel permeation chromatography, and electron microscopy. The clearance and metabolism of the complexes were studied in nude mice. RESULTS PAGE and gel permeation chromatography showed that more than 70% of the antibodies formed complexes. The electron microscopy studies revealed that the complexes formed between TS1 and αTS1 are mainly ring‐shaped (66.6–73.4%), comprising 4 to > 8 antibodies. These rings consist of equal numbers of idiotype and anti‐idiotype. The most commonly observed complexes were tetrameric rings (26.8–40.5%), hexameric rings (10.7–11.9%), and rings containing more than eight monoclonal antibodies (6.6–14‐4%). The in vivo study illustrated that within 24 hours 80% of the total nuclide content had been degraded and excreted via the urine, compared with 25% for similarly treated mice that did not receive any anti‐idiotype. CONCLUSIONS Interestingly, the electron microscopy study demonstrated that dimers were rare (0.4–1.2%), probably reflecting a location of epitopes incompatible with tight, sterically constrained dimeric interactions; insufficient flexibility of the immunoglobulin G1 subtype hinge regions; or both. The anti‐idiotypic clearing mechanisms proved efficient in nude mice. In vivo metabolic studies indicate that the accumulation and degradation of TS1/αTS1 immune complexes, to a large extent, take place in the liver, where a substantial amount was detected as soon as 1 hour after anti‐idiotype injection. Cancer 2002;94:1306–13. © 2002 American Cancer Society. DOI 10.1002/cncr.10301