The T cell-dependent B cell immune response and germinal center reaction are intact in A-myb-deficient mice

Expression of the protooncogene A-myb is restricted to the developing CNS, adult testes, breasts in late pregnancy, and germinal centers of secondary B cell follicles. The functional relevance of A-myb expression at three of these sites has been demonstrated previously via the generation and analysis of A-myb-deficient mice, which display behavioral abnormalities, male sterility, and perturbed breast development during pregnancy. In contrast, here we show that the germinal center response driven by T cell-dependent Ag immunization and the associated processes of Ab V gene somatic hypermutation, affinity maturation, and heavy chain class switching are overtly normal in A-myb-deficient mice. Nonetheless, these mice display mild splenic white pulp hypoplasia and blunted primary serum Ab responses, suggesting that although A-myb is not directly involved in the regulation of the memory B cell response, it may play a role in enhancing peripheral B cell survival or proliferative capacity.     

Change in Brain Magnetic Resonance Spectroscopy after Treatment during Acute HIV Infection

Objective

Single voxel proton magnetic resonance spectroscopy (MRS) can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART).

Methods

Brain metabolite levels of N-acetyl aspartate (NAA), choline (tCHO), creatine (CR), myoinositol (MI), and glutamate and glutamine (GLX) were measured in acute HIV subjects (n = 31) and compared to chronic HIV+individuals (n = 26) and HIV negative control subjects (n = 10) from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM), frontal white matter (FWM), occipital gray matter (OGM), and basal ganglia (BG). Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART.

Results

After adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection) compared to control (p = 0.0014), as well as chronic subjects (p = 0.0023). A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022) with tCHO/CR similar to control subjects at 6 months.

Interpretation

We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury.     

Gene transfer in swine embryos by injection of cells infected with retrovirus vectors

Key components for gene transfer to swine embryos using an avian retrovirus are described. A replication-defective reticuloendotheliosis (REV) viral vector can infect and be expressed in pig embryo fibroblasts (PEF). Infection with a replication-competent vector (REV-A) indicates a presumptive block to viral replication in PEF. Swine embryos obtained at the morula stage can be cultured in vitro to the blastocyst stage, injected with retrovirus helper cells or quail embryo fibroblasts producing REV, and transferred to recipient swine with survival to at least 6 wk of gestation.     

Reproductive performance and mutagenic response of the wasp Bracon hebetor following treatment with the antibiotic bleomycin

Bleomycin (BM) induced dominant-lethal genetic lesions in the gametes of both sexes of adult Bracon hebetor wasps following ingestion. This effect was demonstrated by decreased fertility in the unfertilized eggs of treated females as well as in eggs fertilized by mature sperm derived from treated males. Death in the unhatched eggs occurred prior to blastoderm formation indicating BM caused chromosome breakage. Affected ovarian cells were limited to those exposed to BM between the developmental stages of vitellogenesis and early metaphase I. Sperm-associated fertility reductions were temporary in duration with substantial reductions being observed starting on the second day following the initiation of oviposition. BM lowered general egg-formation capacity in treated females but, unlike the fertility effects, decreased fecundity was caused by somatic debility. Although the BM-induced genetic damage observed in B. hebetor was radiomimetic in nature, the time of appearance and duration of the effects did not correspond with previous patterns found when B. hebetor adults were exposed to X-rays. While the differences could be due to the BM detoxification or the repair of BM-induced chromosome damage, further investigation would be required to demonstrate the presence of such systems in this hymemopteran.