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

HIV-1 感染早期的多克隆 B 细胞分化和胃肠道生发中心的丧失

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作者:Marc C Levesque, M Anthony Moody, Kwan-Ki Hwang, Dawn J Marshall, John F Whitesides, Joshua D Amos, Thaddeus C Gurley, Sallie Allgood, Benjamin B Haynes, Nathan A Vandergrift, Steven Plonk, Daniel C Parker, Myron S Cohen, Georgia D Tomaras, Paul A Goepfert, George M Shaw, Jörn E Schmitz, Joseph J Er

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.

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.

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