title: Appearance of immature/transitional B cells in HIV-infected individuals with advanced disease: correlation with increased IL-7.
abstract: 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.
authors.affiliation: Laboratory of Immunoregulation, and Office of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Malaspina
authors.forename: Susan
authors.initials: S
authors.lastname: Moir
authors.forename: Jason
authors.initials: J
authors.lastname: Ho
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Howell
authors.forename: Marie A
authors.initials: MA
authors.lastname: O'Shea
authors.forename: Gregg A
authors.initials: GA
authors.lastname: Roby
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Rehm
authors.forename: Joann M
authors.initials: JM
authors.lastname: Mican
authors.forename: Tae-Wook
authors.initials: TW
authors.lastname: Chun
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Fauci
mesh_terms: D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D023201:CD40 Ligand / Q000494:pharmacology; D049109:Cell Proliferation; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D015851:Interleukin-7 / Q000097:blood* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008231:Lymphopenia / Q000276:immunology; D015260:Neprilysin / Q000032:analysis*; D015854:Up-Regulation
chemical_list: D015851:Interleukin-7; D023201:CD40 Ligand; D015260:Neprilysin