Appearance of Immature/Transitional B Cells in HIV-Infected Individuals with Advanced Disease: Correlation with Increased IL-7

Progression of HIV disease is associated with the appearance of numerous B cell defects. We describe herein a population of immature/transitional B cells that is overly represented in the peripheral blood of individuals with advancing HIV disease. These B cells, identified by the expression of CD10,...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2006-02, Vol.103 (7), p.2262-2267
Main Authors: Malaspina, Angela, Moir, Susan, Ho, Jason, Wang, Wei, Howell, Melissa L., O'Shea, Marie A., Roby, Gregg A., Rehm, Catherine A., Mican, JoAnn M., Chun, Tae-Wook, Fauci, Anthony S.
Format: Article
Language:English
Subjects:
AIDS
B lymphocytes
B-Lymphocytes - drug effects
B-Lymphocytes - immunology
Biological Sciences
Blood
Blood plasma
CD40 Ligand - pharmacology
Cell Proliferation
Cells
Epidemiology
Gene expression
HIV
HIV Infections - immunology
HIV-1
Human immunodeficiency virus
Humans
Interleukin-7 - blood
Interleukin-7 - metabolism
Lymphocyte Activation - immunology
Lymphopenia - immunology
Memory
Neprilysin - analysis
Neurons
Receptors
T lymphocytes
Up-Regulation
Viremia
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Summary:Progression of HIV disease is associated with the appearance of numerous B cell defects. We describe herein a population of immature/transitional B cells that is overly represented in the peripheral blood of individuals with advancing HIV disease. These B cells, identified by the expression of CD10, were unresponsive by proliferation to B cell receptor triggering and possessed a phenotype and an Ig diversity profile that confirmed their immature/ transitional stage of differentiation. Consistent with an immature status, their lack of proliferation to B cell receptor triggering was reversed with CD40 ligand, but not B cell activation factor. Finally, levels of CD10 expression on B cells were directly correlated with serum levels of IL-7, suggesting that increased levels of IL-7 modulate human B cell maturation either directly or indirectly by means of a homeostatic effect on lymphopenia. Taken together, these data offer insight into human B cell development as well as B cell dysfunction in advanced HIV disease that may be linked to IL-7-dependent homeostatic events.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0511094103