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

• 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
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0511094103

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.