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Bone marrow plasma cells are a primary source of serum HIV-1-specific antibodies in chronically infected individuals.

Authors :
Montezuma-Rusca JM
Moir S
Kardava L
Buckner CM
Louie A
Kim LJ
Santich BH
Wang W
Fankuchen OR
Diaz G
Daub JR
Rosenzweig SD
Chun TW
Li Y
Braylan RC
Calvo KR
Fauci AS
Source :
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2015 Mar 15; Vol. 194 (6), pp. 2561-8. Date of Electronic Publication: 2015 Feb 13.
Publication Year :
2015

Abstract

Several potent and broadly neutralizing Abs to HIV-1 have been isolated recently from peripheral blood B cells of infected individuals, based on prescreening of Ab activity in the serum. However, little is known regarding the cells that make the Abs that circulate in the blood. Accordingly, we investigated the most likely source, the bone marrow, of chronically HIV-1-infected individuals who were not receiving antiretroviral therapy. Increased frequencies of plasma cells, as well as B cell precursors, namely preB-I and preB-II, and decreased frequencies of mature B cells were observed in bone marrow aspirates of these individuals compared with HIV-negative counterparts. Increased frequencies of bone marrow plasma cells are consistent with known hallmarks of HIV-1 infection, namely hypergammaglobulinemia and increased frequencies of peripheral blood plasmablasts. Levels of HIV-1 envelope (Env)-binding and HIV-1-neutralizing Abs were measured in serum, and corresponding frequencies of Ab-secreting or Env-binding cells were measured in the blood (plasmablasts and memory B cells) and in the bone marrow (plasma cells). A strong correlation was observed between serum HIV-1-specific Abs and Env-specific bone marrow-derived plasma cells, but not circulating plasmablasts or memory B cells. These findings demonstrate that, despite HIV-1-induced phenotypic and functional B cell dysregulation in the peripheral blood and secondary lymphoid tissues, bone marrow plasma cells remain a primary source for circulating HIV-1-specific Abs in HIV-1-infected individuals.

Details

Language :
English
ISSN :
1550-6606
Volume :
194
Issue :
6
Database :
MEDLINE
Journal :
Journal of immunology (Baltimore, Md. : 1950)
Publication Type :
Academic Journal
Accession number :
25681347
Full Text :
https://doi.org/10.4049/jimmunol.1402424