Intrinsic differences in the proliferation of naive and memory human B cells as a mechanism for enhanced secondary immune responses

Humoral immune responses elicited after secondary exposure to immunizing Ag are characterized by robust and elevated reactivity of memory B cells that exceed those of naive B cells during the primary response. The mechanism underlying this difference in responsiveness of naive vs memory B cells remains unclear. We have quantitated the response of naive and memory human B cells after in vitro stimulation with T cell-derived stimuli. In response to stimulation with CD40 ligand alone or with IL-10, both IgM-expressing and Ig isotype-switched memory B cells entered their first division 20-30 h earlier than did naive B cells. In contrast, the time spent traversing subsequent divisions was similar. Consistent with previous studies, only memory cells differentiated to CD38(+) blasts in a manner that increased with consecutive division number. These differentiated CD38(+) B cells divided faster than did CD38(-) memory B cell blasts. Proliferation of CD40 ligand-stimulated naive B cells as well as both CD38(+) and CD38(-) cells present in cultures of memory B cells was increased by IL-10. In contrast, IL-2 enhanced proliferation of CD38(-) and CD38(+) memory B cell blasts, but not naive cells. Thus, memory B cells possess an intrinsic advantage over naive B cells in both the time to initiate a response and in the division-based rate of effector cell development. These differences help explain the accelerated Ab response exhibited by memory B cells after secondary challenge by an invading pathogen, a hallmark of immunological memory.     

Self-reactive, T cell receptor-gamma delta+, lymphocytes from the intestinal epithelium of weanling mice.

Intraepithelial T lymphocytes (IEL) are dispersed throughout the intestinal epithelial lining but their role in cellular immune defense is unknown. Their location suggests that their highly activated state may be due to constant exposure to bacterial Ag. To study IEL specificity and function we have prepared a panel of IEL-T cell hybridomas from both adult and weanling C57B1/6 mice. Many of these expressed TCR-gamma delta, a cell type rare in peripheral lymph nodes and spleen but predominant at epithelial surfaces. We have identified a subset of gamma delta T cells from weanling mice which is self reactive, i.e., these hybrids secrete IL-2 spontaneously, without antigenic stimulation or a requirement for APC. Self-reactive TCR-gamma delta+ hybrids and lines, all of which bear a particular TCR (V gamma 1.1C gamma 4V delta 6), have previously been derived from neonatal thymus and the skin. Northern blot and immunoprecipitation analyses suggest that the self-reactive IEL hybrids also bear a C gamma 4/V delta 6 TCR. Antibody inhibition experiments showed that the self-reactivity of the IEL hybrids is TCR mediated. Spontaneous IL-2 production was blocked by soluble anti-CD3 and anti-TCR-gamma delta antibodies but not by antibodies to the TCR-alpha beta. The self-reactive IEL hybrids lack class II MHC and the class I-like proteins CD1 and TLA but express class I MHC. IEL hybrids may also require the vitronectin receptor as an accessory molecule for their activation because spontaneous IL-2 production is blocked by antibody to the vitronectin receptor as well as by the extracellular matrix protein active site peptide RGDS, but not the control peptide RGES. V gamma 1.1C gamma 4V delta 6 T cells in the thymus, skin, and intestine may represent a small and unique subpopulation of lymphocytes with a potential for autoimmune reactivity at peripheral sites.     

The Value of Forests to World Food Security

We assembled information on the contribution and value of forests to world food security. An assessment was made of the role of forests and non-timber products in the food system of developing countries. We estimated that upwards of 300 million people annually earn part or all of their livelihood and food from forests. A total of about $90 billion in non-timber products are harvested each year. Forests also help to protect land, water, and biological resources, and they play an important role in maintaining the productivity of agricultural and environmental systems.     

Cadmium induces a heterogeneous and caspase-dependent apoptotic response in <Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis>

The toxic metal cadmium is linked to a series of degenerative disorders in humans, in which Cd-induced programmed cell death (apoptosis) may play a role. The yeast, Saccharomyces cerevisiae, provides a valuable model for elucidating apoptosis mechanisms, and this study extends that capability to Cd-induced apoptosis. We demonstrate that S. cerevisiae undergoes a glucose-dependent, programmed cell death in response to low cadmium concentrations, which is initiated within the first hour of Cd exposure. The response was associated with induction of the yeast caspase, Yca1p, and was abolished in a yca1Δ mutant. Cadmium-dependent apoptosis was also suppressed in a gsh1Δ mutant, indicating a requirement for glutathione. Other apoptotic markers, including sub-G₁ DNA fragmentation and hyper-polarization of mitochondrial membranes, were also evident among Cd-exposed cells. These responses were not distributed uniformly throughout the cell population, but were restricted to a subset of cells. This apoptotic subpopulation also exhibited markedly elevated levels of intracellular reactive oxygen species (ROS). The heightened ROS levels alone were not sufficient to induce apoptosis. These findings highlight several new perspectives to the mechanism of Cd-dependent apoptosis and its phenotypic heterogeneity, while opening up future analyses to the power of the yeast model system.     

Force-velocity analysis of strength-training techniques and load: implications for training strategy and research

The purpose of this study was to investigate the force-velocity response of the neuromuscular system to a variety of concentric only, stretch-shorten cycle, and ballistic bench press movements. Twenty-seven men of an athletic background (21.9 +/- 3.1 years, 89.0 +/- 12.5 kg, 86.3 +/- 13.6 kg 1 repetition maximum [1RM]) performed 4 types of bench presses, concentric only, concentric throw, rebound, and rebound throw, across loads of 30-80% 1RM. Average force output was unaffected by the technique used across all loads. Greater force output was recorded using higher loading intensities. The use of rebound was found to produce greater average velocities (12.3% higher mean across loads) and peak forces (14.1% higher mean across loads). Throw or ballistic training generated greater velocities across all loads (4.4% higher average velocity and 6.7% higher peak velocity), and acceleration-deceleration profiles provided greater movement pattern specificity. However, the movement velocities (0.69-1.68 m.s(-1)) associated with the loads used in this study did not approach actual movement velocities associated with functional performance. Suggestions were made as to how these findings may be applied to improve strength, power, and functional performance.     

Chromosomes and their relationship to nuclear components during the cell cycle in Chinese hamster cells

Summary Chromosomes and their relationship to nuclear components during various phases of the cell cycle were studied with different fixation, embedding, and enzyme techniques. The results showed that interphase chromosomes may have oriented in such a way that a given locus became associated with the nuclear membrane. Some chromosomes also appeared to interact with the nucleolus. The nuclear matrix materials, however, were distributed between the chromosomes and formed a delineating boundary for the chromosomes. These matrix materials, furthermore, formed channel-like structures within the nucleus and towards the cytoplasm through their interaction with nuclear pore complexes. During mitosis, chromosomes were encapsulated with material that appeared to be derived from the matrix, disintegrated residues and fragments of the nuclear envelope, the lamina, and nucleolar material. These chromosome-associated materials seen in mitosis appeared to serve as foci for formation of new nuclear components in subsequent interphase.     

Self-selected resistance training intensity in healthy women: the influence of a personal trainer

The purpose of the present investigation was to examine the influence of resistance training with a personal trainer versus unsupervised resistance training on the self-selected intensities used by women during resistance exercise. Forty-six resistance-trained women (age = 26.6 +/- 6.4 years; body mass = 64.2 +/- 10.9 kg) who either trained individually (n = 27; No PT) or with a personal trainer (n = 19; PT) were carefully instructed to select a weight they used in their own resistance training workouts that enabled the completion of 10 repetitions for the chest press (CP), leg press (LP), seated row (SR), and leg extension (LE) exercises. Each participant was subsequently tested for one repetition-maximum (1RM) strength on each exercise, and the self-selected intensity was calculated based on a percent of each 1RM value. For self-selected relative intensity, the PT group selected significantly greater intensities for LP (50% vs. 41%), CP (57.4% vs. 48%), and SR (56% vs. 42%) whereas a trend (p = 0.10) was observed for LE (43% vs. 38%) compared with No PT. Overall, the average self-selected intensity for all exercises was approximately 51.4% in PT group and approximately 42.3% in the No PT group. 1RM values for LP, LE, and SR were greater in the PT than No PT group. Ratings of perceived exertion values were significantly greater in the PT compared with the No PT group for CP, LE, and SR but not LP. These results indicate that resistance training under the supervision of a personal trainer leads to greater initial 1RM strength values, self-selection of greater workout intensities, and greater ratings of perceived exertion values during resistance exercise.     

The Cognitive Control of Memory: Age Differences in the Neural Correlates of Successful Remembering and Intentional Forgetting

Successful memory encoding depends on the ability to intentionally encode relevant information (via differential encoding) and intentionally forget that which is irrelevant (via inhibition). Both cognitive processes have been shown to decline in aging and are theorized to underlie age-related deficits in the cognitive control of memory. The current study uses the Directed Forgetting paradigm in conjunction with fMRI to investigate age-related differences in both cognitive processes, with the specific aim of elucidating neural evidence supporting these theorized deficits. Results indicate relatively preserved differential encoding, with age differences consistent with previous models of age-related compensation (i.e., increased frontal and bilateral recruitment). Older adults did display noticeable differences in the recruitment of brain regions related to intentional forgetting, specifically exhibiting reduced activity in the right superior prefrontal cortex, a region shown to be critical to inhibitory processing. However, older adults exhibited increased reliance on processing in right inferior parietal lobe associated with successful forgetting. Activity in this region was negatively correlated with activity in the medial temporal lobe, suggesting a shift in the locus of inhibition compared to the frontally mediated inhibition observed in younger adults. Finally, while previous studies found intentional and incidental forgetting to be dissociable in younger adults, this differentiation appears to be reduced in older adults. The current results are the first to provide neural evidence for an age-related reduction in processes that support intentional forgetting.     

Signal transduction via the T cell antigen receptor in naïve and effector/memory T cells

T cells play an indispensable role in immune defense against infectious agents, but can also be pathogenic. These T cells develop in the thymus, are exported into the periphery as naïve cells and participate in immune responses. Upon recognition of antigen, they are activated and differentiate into effector and memory T cells. While effector T cells carry out the function of the immune response, memory T cells can last up to the life time of the individual, and are activated by subsequent antigenic exposure. Throughout this life cycle, the T cell uses the same receptor for antigen, the T cell Receptor, a complex multi-subunit receptor. Recognition of antigen presented by peptide/MHC complexes on antigen presenting cells unleashes signaling pathways that control T cell activation at each stage. In this review, we discuss the signals regulated by the T cell receptor in naïve and effector/memory T cells.