Biology Reference
In-Depth Information
F i g u r e 5.8. Extracellular Tat increases CD95 expression on BCR-triggered naive B cells. Naive
(IgD
) B cells were stimulated for 2 days by anti-IgM Ab and IL-4 in the presence or absence of
wild-type Tat (1 mg/mL). Unstimulated (D0) and day 2-activated B cells were stained with CD20-
FITC (¯uorescein isothiocyanate) or CD95-PE (phycoerythrin) mAb. Data are representative of
three independent experiments.
ation and Ig production, only Ig production is inhibited by Tat. Tat decreases
IgA, IgG, and IgM production by 40±60% without impairing CD40-induced
isotype switching. This suggests that Tat decreases the survival or terminal dif-
ferentiation of plasma cells.
As Tat exerts some of its biological activity by interfering with cytokine
production ( Rubartelli et al., 1998), we assessed its e¨ect on the production of
several B-cell-derived cytokines. No signi®cant change in IL-8, IL-10, and
TGF-b production was observed after Tat addition in our experimental con-
ditions. The addition of Tat slightly a¨ected the production of MIP-1a, MIP-
1b, TNF-a, and IL-6 in CD40 mAb and IL-4-stimulated cultures but strongly
decreased their production in anti-IgM Ab-stimulated cultures. It seems un-
likely that Tat controls B-cell proliferation via the modulation of cytokines be-
cause: (i) Tat increases CD40 mAb and IL-4-induced cell proliferation but not
cytokine production and (ii) addition of recombinant MIP-1a, MIP-1b, TNF-a,
or IL-6 does not abolish the Tat-induced inhibition of anti-IgM proliferation.
However, the low level of MIP-1a and MIP-1b production may impair the re-
cruitment of CD4
CD45RO
helper T cells and interfere with T/B interac-
tions, leading to abnormal T-cell-dependent maturation of the B-cell response
