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, 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.
Malaspina
Angela
A
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.
Moir
Susan
S
Ho
Jason
J
Wang
Wei
W
Howell
Melissa L
ML
O'Shea
Marie A
MA
Roby
Gregg A
GA
Rehm
Catherine A
CA
Mican
Joann M
JM
Chun
Tae-Wook
TW
Fauci
Anthony S
AS
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
D015851:Interleukin-7; D023201:CD40 Ligand; D015260:Neprilysin