Polyclonal B cell differentiation and loss of gastrointestinal tract germinal centers in the earliest stages of HIV-1 infection.

BACKGROUND: The antibody response to HIV-1 does not appear in the plasma until approximately 2-5 weeks after transmission, and neutralizing antibodies to autologous HIV-1 generally do not become detectable until 12 weeks or more after transmission. Moreover, levels of HIV-1-specific antibodies decline on antiretroviral treatment. The mechanisms of this delay in the appearance of anti-HIV-1 antibodies and of their subsequent rapid decline are not known. While the effect of HIV-1 on depletion of gut CD4(+) T cells in acute HIV-1 infection is well described, we studied blood and tissue B cells soon after infection to determine the effect of early HIV-1 on these cells. METHODS AND FINDINGS: In human participants, we analyzed B cells in blood as early as 17 days after HIV-1 infection, and in terminal ileum inductive and effector microenvironments beginning at 47 days after infection. We found that HIV-1 infection rapidly induced polyclonal activation and terminal differentiation of B cells in blood and in gut-associated lymphoid tissue (GALT) B cells. The specificities of antibodies produced by GALT memory B cells in acute HIV-1 infection (AHI) included not only HIV-1-specific antibodies, but also influenza-specific and autoreactive antibodies, indicating very early onset of HIV-1-induced polyclonal B cell activation. Follicular damage or germinal center loss in terminal ileum Peyer's patches was seen with 88% of follicles exhibiting B or T cell apoptosis and follicular lysis. CONCLUSIONS: Early induction of polyclonal B cell differentiation, coupled with follicular damage and germinal center loss soon after HIV-1 infection, may explain both the high rate of decline in HIV-1-induced antibody responses and the delay in plasma antibody responses to HIV-1. Please see later in the article for Editors' Summary.

Forefoot loading during 3 athletic tasks.

BACKGROUND: Due to the popularity of soccer and the high incidence of injury among soccer players, it is valuable to know the effects of tasks like side cuts, crossover cuts, and forward acceleration on the foot. PURPOSE: To determine the differences in forefoot loading during three different athletic tasks. STUDY DESIGN: Descriptive laboratory study. METHODS: Thirty-six subjects (17 women and 19 men) were tested. Subjects ran a slalom-style agility course 5 times while plantar pressure data was collected at 100 Hz. Plantar pressure was recorded under both feet; however, a right-foot contact was used in the analysis of the side-cut task, a left-foot plant was used in the analysis of the crossover cut, and an average of the 3 steps of acceleration were used in the analysis. The peak pressure, contact area, and contact time for the entire foot were compared between the 3 tasks. The force and the force-time integral were obtained during 5 trials for each of the 3 tasks. The foot was divided into 8 masked regions, which were used to determine the loading patterns specifically in the forefoot. Each variable was analyzed using a 1 x 3 analysis of variance to determine differences between the three movement tasks in the forefoot region (a = .05). RESULTS: Significant differences in peak pressure, contact area, and contact time existed between the movement tasks when examining the entire foot. In addition, significant differences in the force-time integral and peak pressure in the forefoot existed between the movement tasks. The force-time integral was highest during the side cut in the medial forefoot, hallux, and the lesser toes, while the force-time integral was highest during the crossover cut in the middle forefoot and the lateral forefoot. Similarly, the peak pressure was highest during the side cut in the medial forefoot, hallux, and the lesser toes, while peak pressure was highest in the middle forefoot during the acceleration task and highest in the lateral forefoot during the crossover-cutting task. CONCLUSIONS: The results of this study demonstrated that the crossover cut places an increased load on the lateral portion of the forefoot, while the side-cut task places an increased load on the medial portion of the forefoot and the acceleration task places increased load on the middle forefoot. CLINICAL RELEVANCE: The differences in loading patterns based on athletic task are important for understanding potential injury mechanisms. In addition, this information could be important for defining a return to play protocol for athletes who have had specific injuries.