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.
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
Susan
S
Moir
Kisani M
KM
Ogwaro
Angela
A
Malaspina
Joshua
J
Vasquez
Eileen T
ET
Donoghue
Claire W
CW
Hallahan
Shuying
S
Liu
Linda A
LA
Ehler
Marie A
MA
Planta
Shyamasundaran
S
Kottilil
Tae-Wook
TW
Chun
Anthony S
AS
Fauci
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