HIV-1 antigen-specific and -nonspecific B cell responses are sensitive to combination antiretroviral therapy

被引:192
作者
Morris, L [1 ]
Binley, JM [1 ]
Clas, BA [1 ]
Bonhoeffer, S [1 ]
Astill, TP [1 ]
Kost, R [1 ]
Hurley, A [1 ]
Cao, YZ [1 ]
Markowitz, M [1 ]
Ho, DD [1 ]
Moore, JP [1 ]
机构
[1] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA
关键词
hypergammaglobulinemia; human immunodeficiency virus 1; B cells; antiretroviral therapy; antibody;
D O I
10.1084/jem.188.2.233
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We studied how combination antiviral therapy affects B cell abnormalities associated with HIV-1 infection, namely elevated circulating immunoglobulin (Ig)G antibody-secreting cell. (ASC) frequencies and hypergammaglobulinemia. Within a few weeks of starting antiviral therapy, there is a marked decline in IgG-ASC frequency in both acutely and chronically infected people, whereas the hypergammaglobulinenlia often present during chronic infection is more gradually resolved. These reductions are sustained while HIV-1 replication is suppressed. HIV-1 antigen-specific B cell responses are also affected by therapy, manifested by a rapid decline in circulating gp120-specific ASCs. Anti-gp120 titers slowly decrease in chronically infected individuals and usually fail to mature in acutely infected individuals who were promptly treated with antiretroviral therapy. Long-term nonprogressors have high titer antibody responses to HIV-1 antigens, but no detectable gp120-specific IgG-ASC, and normal (or subnormal) levels of total circulating IgG-ASC. Overall, we conclude that HIV-1 infection drives B cell hyperactivity, and that this polyclonal activation is rapidly responsive to decreases in viral replication caused by combination antiviral therapy.
引用
收藏
页码:233 / 245
页数:13
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