Research Article: Polyclonal B Cell Differentiation and Loss of Gastrointestinal Tract Germinal Centers in the Earliest Stages of HIV-1 Infection

Date Published: July 7, 2009

Publisher: Public Library of Science

Author(s): 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. Eron, Nicholas J. Shaheen, Charles B. Hicks, Hua-Xin Liao, Martin Markowitz, Garnett Kelsoe, David M. Margolis, Barton F. Haynes, H. Clifford Lane

Abstract: Studying the effects of early HIV infection on human antibody responses, M. Anthony Moody and colleagues find rapid polyclonal B cell differentiation and structural damage to gut-associated lymphoid tissue.

Partial Text: Early HIV-1 infection is characterized by the death of both infected and uninfected CD4+ T cells, often resulting in extensive CD4+ T cell depletion in the gastrointestinal tract [1]–[6]. While HIV-1 induction of CD4+ T cell death in early infection is well documented, the effects of HIV-1 on blood and mucosal B cells and their inductive microenvironments in the earliest stages of infection have not been determined. In chronic infection, HIV-1 induces polyclonal B-cell activation, B cell exhaustion, hypergammaglobulinemia, reductions in the numbers of memory B cells in the blood, and increased numbers of circulating immature B cells [7]–[12]. People with early HIV-1 infection have elevated frequencies of blood antibody-secreting cells that may reflect Env-mediated polyclonal activation [10],[13],[14], but have been reported to have normal numbers of blood naïve and memory B cells [15].

By as early as 17 d after transmission, HIV-1 infection induced B cell class switching manifested by acute reductions in numbers of naïve B cells and striking elevations of memory B cells and plasmablasts/plasma cells in blood and terminal ileum. By 47 d after transmission, HIV-1 infection was associated with damage to GALT germinal centers, including follicular lysis due to B and T cell apoptosis as well as destruction of the FDC networks in terminal ileum Peyer’s patches.

Source:

http://doi.org/10.1371/journal.pmed.1000107

 

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