Browsing by Author "Foulger, A"

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    HIV-1 envelope gp41 antibodies can originate from terminal ileum B cells that share cross-reactivity with commensal bacteria.
    (Cell Host Microbe, 2014-08-13) Trama, A; Moody, MA; Alam, SM; Jaeger, F; Lockwood, B; Parks, R; Lloyd, K; Stolarchuk, C; Scearce, R; Foulger, A; Marshall, D; Whitesides, J; Jeffries, T; Wiehe, K; Morris, L; Lambson, B; Soderberg, K; Hwang, K; Tomaras, G; Vandergrift, N; Jackson, KL; Roskin, K; Boyd, S; Kepler, T; Liao, H; Haynes, B
    Monoclonal antibodies derived from blood plasma cells of acute HIV-1-infected individuals are predominantly targeted to the HIV Env gp41 and cross-reactive with commensal bacteria. To understand this phenomenon, we examined anti-HIV responses in ileum B cells using recombinant antibody technology and probed their relationship to commensal bacteria. The dominant ileum B cell response was to Env gp41. Remarkably, a majority (82%) of the ileum anti-gp41 antibodies cross-reacted with commensal bacteria, and of those, 43% showed non-HIV-1 antigen polyreactivity. Pyrosequencing revealed shared HIV-1 antibody clonal lineages between ileum and blood. Mutated immunoglobulin G antibodies cross-reactive with both Env gp41 and microbiota could also be isolated from the ileum of HIV-1 uninfected individuals. Thus, the gp41 commensal bacterial antigen cross-reactive antibodies originate in the intestine, and the gp41 Env response in HIV-1 infection can be derived from a preinfection memory B cell pool triggered by commensal bacteria that cross-react with Env.