Restricted isotype, distinct variable gene usage, and high rate of gp120 specificity of HIV-1 envelope-specific B cells in colostrum compared with those in blood of HIV-1-infected, lactating African women.

A successful HIV-1 vaccine must elicit immune responses that impede mucosal virus transmission, though functional roles of protective HIV-1 Envelope (Env)-specific mucosal antibodies remain unclear. Colostrum is a rich source of readily accessible mucosal B cells that may help define the mucosal antibody response contributing to prevention of postnatal HIV-1 transmission. To examine the HIV-1 Env-specific colostrum B-cell repertoire, single B cells were isolated from 17 chronically HIV-infected, lactating women, producing 51 blood and 39 colostrum HIV-1 Env-specific B-cell antibodies. All HIV-1 Env-specific colostrum-derived antibodies were immunoglobulin (Ig)G1 isotype and had mean heavy chain complementarity-determining region 3 (CDR3) lengths and mutation frequencies similar to those isolated from blood. However, variable heavy chain (VH) gene subfamily 1(∼)69 usage was higher among colostrum than blood HIV-1 Env-reactive antibodies (49% vs. 20%, P=0.006, Fisher's exact test). Additionally, more HIV-1 Env-specific colostrum antibodies were gp120 specific than those isolated from blood (44% vs. 16%, P=0.005, Fisher's exact test). One cross-compartment HIV-1 Env-specific clonal B-cell lineage was identified. These unique characteristics of colostrum B-cell antibodies suggest selective homing of HIV-1-specific IgG1-secreting memory B cells to the mammary gland and have implications for targeting mucosal B-cell populations by vaccination.

HIV-1 gp41 envelope IgA is frequently elicited after transmission but has an initial short response half-life.

Prevention of HIV-1 transmission at mucosal surfaces will likely require durable pre-existing mucosal anti-HIV-1 antibodies (Abs). Defining the ontogeny, specificities and potentially protective nature of the initial mucosal virus-specific B-cell response will be critical for understanding how to induce protective Ab responses by vaccination. Genital fluids from patients within the earliest stages of acute HIV-1 infection (Fiebig I-VI) were examined for multiple anti-HIV specificities. Gp41 (but not gp120) Env immunoglobulin (Ig)A Abs were frequently elicited in both plasma and mucosal fluids within the first weeks of transmission. However, shortly after induction, these initial mucosal gp41 Env IgA Abs rapidly declined with a t(½) of ∼2.7 days. B-cell-activating factor belonging to the TNF family (BAFF) was elevated immediately preceding the appearance of gp41 Abs, likely contributing to an initial T-independent Ab response. HIV-1 transmission frequently elicits mucosal HIV-1 envelope-specific IgA responses targeted to gp41 that have a short half-life.

Language comprehension in boys with fragile X syndrome and boys with Down syndrome.

BACKGROUND: Fragile X syndrome (FXS) is the most common known inherited cause of intellectual disability, yet very few studies have explored the language comprehension skills of children with FXS. We examined the receptive vocabulary, grammatical morphology and syntax skills of boys with FXS (who were additionally classified as having autism, autism spectrum, or no autism) and compared them to boys with Down syndrome (DS) and typically developing (TD) boys at similar non-verbal developmental levels. METHODS: The Vocabulary, Grammatical Morphology, and Elaborated Phrases and Sentences subtests of the Test for Auditory Comprehension of Language - 3rd Edition (TACL-3) were administered annually up to three times to assess the language comprehension skills of 35 boys with FXS without autism, 24 boys with FXS with autism spectrum, 19 boys with FXS with autism, 45 boys with DS and 40 TD boys at similar non-verbal cognitive levels. RESULTS: After controlling for non-verbal cognition and maternal education levels, we found that the three groups of boys with FXS did not differ from each other but scored lower than the TD boys in language comprehension. The boys with DS scored lower in language comprehension than boys with FXS without autism and TD boys. For all of the groups, scores for receptive vocabulary, grammatical morphology and syntax did not differ. CONCLUSIONS: Boys with FXS and boys with DS differed in receptive language levels, demonstrating unique language profiles for each syndrome. Language comprehension appears to be an important area to target in assessment and intervention for both populations.