A novel putative helicase produced in early murine lymphocytes.

DNA helicases (Hel) play a role in a number of processes involving DNA strand separation, including replication, repair, recombination and transcription. Rearrangement of receptor genes, which occurs in immature lymphocytes, could also be mediated by Hel. We report here the cloning from murine fetal thymus tissue of a novel putative Hel containing seven conserved Hel domains and belonging to the DEGH subclass of DNA Hel. We term the encoding gene lsh (lymphoid-specific Hel), since the gene is expressed in early thymocytes, but not in heart, liver, lung, muscle, brain or kidney, as judged by Northern analysis. Spleen cells expressed lsh following activation. T- and B-cell lines, at both the immature and mature stage, expressed lsh. To examine the earliest stages of lymphopoiesis, mouse embryonic tissues were examined; lsh was not detected in the yolk sac of day 12 of gestation, but was expressed in fetal liver and at high levels in fetal thymus at day 15 of gestation.

Tissue-specific expression of messenger RNAs encoding endogenous viral superantigens.

The minor lymphocyte stimulating (MLS) superantigens of mice are encoded by open reading frames (ORFs) in the 3' long terminal repeats (LTRs) of endogenous mouse mammary tumor viruses. By stimulating all T cells bearing particular TCR V beta proteins, these viral superantigens (v-SAGs) exert profound effects on T cell development and function. We have examined expression of the 1.7 kb mRNA product predicted to encode v-SAG proteins in different cells and tissues of the immune system. The LTR-ORF mRNA was expressed in activated B cells and activated mature CD8 but not CD4 T cells, consistent with previous functional studies assessing MLS activity in these cell types. Little or no message was detected in thymic epithelial cells, macrophages, or dendritic cells, although low levels could be observed in thymic epithelium after southern hybridization to PCR-amplified cDNA. LTR-ORF mRNA was also expressed in immature CD4-CD8- and CD4+CD8+ thymocytes, suggesting selective down-regulation of expression in the T cell lineage after differentiation to the CD4+ phenotype. Thus, among cells of the immune system, v-SAG encoding mRNA is expressed predominantly within the lymphoid lineage.

Mouse antibody response to group A streptococcal carbohydrate.

In an attempt to more fully understand the generation of antibody diversity to carbohydrate (CHO) Ag, we produced and characterized a panel of hybridoma cell lines specific for group A streptococcal CHO from mice injected with the intact bacteria (minus the hyaluronic acid capsule and cell wall protein Ag). We have analyzed the use of H and L chain V region genes in the early (day 7) and late response (hyperimmune) and have sequenced the dominant VH gene used in several of our hybridomas. Our data allowed us to assess the extent to which the recombination of various V, D, and J gene segments and somatic mutation contribute to antibody diversification in this system. In this report we confirm that a minimum of two VH and four VK gene segments are used to encode this response. We extend this analysis to show that multiple D and J gene segments are used and that a significant amount of junctional variability is tolerated in CDR 3. Our results indicate that the level of somatic mutation in the hyperimmune response is generally low in comparison with the response to haptens and protein Ag. These data also suggest that there is a positive selection for mutation in CDR 1 during the hyperimmune response to group A streptococcal CHO.

Mapping the primate visual system with [2-14C]deoxyglucose.

The [2-14C]deoxyglucose method was used to identify the cerebral areas related to vision in the rhesus monkey (Macaca mulatta). This was achieved by comparing glucose utilization in a visually stimulated with that in a visually deafferented hemisphere. The cortical areas related to vision included the entire expanse of striate, prestriate, and inferior temporal cortex as far forward as the temporal pole, the posterior part of the inferior parietal lobule, and the prearcuate and inferior prefrontal cortex. Subcortically, in addition to the dorsal lateral geniculate nucleus and superficial layers of the superior colliculus, and structures related to vision included large parts of the pulvinar, caudate, putamen, claustrum, and amygdala. These results, which are consonant with a model of visual function that postulates an occipito-temporo-prefrontal pathway for object vision and an occipito-parieto-prefrontal pathway for spatial vision, reveal the full extent of those pathways and identify their points of contact with limbic, striatal, and diencephalic structures.

Pattern discrimination thresholds after partial inferior temporal or lateral striate lesions in monkeys.

Ablation of inferior temporal (IT) cortex, particularly of the posterior region, produces severe impairment in pattern discrimination learning. The present study examined whether this impairment is associated with raised pattern discrimination thresholds. Groups of three monkeys each were given either anterior IT, posterior IT, or foveal striate lesions, or kept as controls. They were trained after surgery on a threshold task in which a 90 degrees white angle on a gray ground was the standard, and 15 angles ranging from 10 degrees through 88.5 degrees were the comparisons. As expected, monkeys with posterior IT lesions were the most severely impaired in learning the initial discrimination (90 degrees vs. 10 degrees). However, only the monkeys with foveal striate lesions showed significant impairment on the subsequent threshold determinations. The results indicate that raised pattern discrimination thresholds are not the cause of the pattern discrimination learning deficits produced by inferior temporal lesions. Data from additional visual discriminations presented after threshold testing was completed point, instead, to a loss of attention to stimulus features as the explanation for the learning deficit.