Perturbations in B cell responsiveness to CD4+ T cell help in HIV-infected individuals.
HIV infection induces a wide array of B cell dysfunctions. We have characterized the effect of plasma viremia on the responsiveness of B cells to CD4(+) T cell help in HIV-infected patients. In HIV-negative donors, B cell proliferation correlated with CD154 expression on activated CD4(+) T cells and with the availability of IL-2, whereas in HIV-infected viremic patients, reduced B cell proliferation was observed despite normal CD154 expression on activated CD4(+) T cells. Reduced triggering of B cells by activated CD4(+) T cells was clearly observed in HIV-infected viremic patients compared with aviremic patients with comparable CD4(+) T cell counts, and a dramatic improvement in B cell function was observed in patients whose plasma viremia was controlled by effective antiretroviral therapy. The degree of B cell dysfunction in viremic patients correlated strongly with the inability of B cells to express CD25 in response to activated CD4(+) T cells, resulting in an inability to mount a normal proliferative response to IL-2. Similar defects in responsiveness to IL-2 were observed in the B cells of HIV-infected viremic patients in the context of B cell receptor stimulation. These data provide new insight into the mechanisms associated with ineffective humoral responses in HIV disease.
Moir
Susan
S
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. smoir@niaid.nih.gov
Ogwaro
Kisani M
KM
Malaspina
Angela
A
Vasquez
Joshua
J
Donoghue
Eileen T
ET
Hallahan
Claire W
CW
Liu
Shuying
S
Ehler
Linda A
LA
Planta
Marie A
MA
Kottilil
Shyamasundaran
S
Chun
Tae-Wook
TW
Fauci
Anthony S
AS
D015703:Antigens, CD / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand / Q000097:blood*; D018929:Cell Culture Techniques; D003430:Cross-Sectional Studies; D005434:Flow Cytometry; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000097:blood / Q000378:metabolism; D008213:Lymphocyte Activation; D012016:Reference Values; D019562:Viral Load; D014766:Viremia / Q000097:blood / Q000276:immunology
D015703:Antigens, CD; D007376:Interleukin-2; D023201:CD40 Ligand