HIV-1 envelope gp41 antibodies can originate from terminal ileum B cells that share cross-reactivity with commensal bacteria.
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.
Trama, AM; Moody, MA; Alam, SM; Jaeger, FH; Lockwood, B; Parks, R; Lloyd, KE; Stolarchuk, C; Scearce, R; Foulger, A; Marshall, DJ; Whitesides, JF; Jeffries, TL; Wiehe, K; Morris, L; Lambson, B; Soderberg, K; Hwang, K-K; Tomaras, GD; Vandergrift, N; Jackson, KJL; Roskin, KM; Boyd, SD; Kepler, TB; Liao, H-X; Haynes, BF
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