Interleukin 4 inhibits the proliferation but not the differentiation of activated human B cells in response to interleukin 2.

Abstract

The combined effect of IL-4 and IL-2 on proliferation of anti-IgM antibody or Staphylococcus aureus strain Cowan I (SAC)-preactivated B cells was investigated. It was observed that in most cases, rIL-2 used at optimal concentration induced higher levels of tritiated thymidine ([3H]TdR) uptake than rIL-4 used at optimal concentration. When rIL-4 and rIL-2 were added together, it was repeatedly found that B cell proliferation induced by rIL-2 was significantly reduced and was, in most cases, comparable with the proliferation induced by rIL-4 alone. Cell cycle studies demonstrated that rIL-4 significantly reduced the number of cells entering S and G2/M phases of the cell cycle upon rIL-2 stimulation. B cell blasts preincubated for 24 or 48 h with rIL-4 displayed a reduced proliferation in response to rIL-2. In contrast, preculture of resting B cells with rIL-4 did not impair their subsequent proliferation in response to rIL-2 plus insolubilized anti-IgM antibody. This suggests that rIL-4 can only exert its inhibitory effect once B cells have received an activation signal. The differentiative activity of rIL-2 measured on B cell blasts preactivated for 2 d with SAC was not altered by rIL-4, which suggests that rIL-4 did not exert its inhibitory activity on rIL-2-induced B cell proliferation by enhancing rIL-2-mediated differentiation. Delayed addition of a neutralizing anti-IL-4 antiserum demonstrated that a period of contact of at least 24 h between IL-4 and B cell blasts was necessary for the development of the antagonistic effect of IL-4 on IL-2-mediated growth of activated B cells. These data demonstrate that IL-4 antagonizes the B cell growth-promoting effect of IL-2 without affecting the differentiation of preactivated B cells in response to IL-2.

CD40 Ligation Inhibits IL‐2 and SAC+IL‐2 Induced Proliferation in Chronic Lymphocytic Leukaemia Cells

“…The inhibition of IL-2þTrx and SACþIL-2þTrx-induced proliferation in I-105 B-CLL cells was found to be a result of an inhibited entrance of the cells into the S-phase of the cell cycle. This inhibition resembles IL-4-induced inhibition of IL-2-dependent proliferation and differentiation of B-CLL and normal B cells [24,31,32].…”

Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes.

“…hIL-10 and vIL-10 gave similar results. Moreover, IL-10 appeared to be more potent than either IL-2 or IL-4, cytokines considered, until now, as the most efficient in this culture system (21).…”

Increased production of soluble CD23 in rheumatoid arthritis, and its regulation by interleukin‐4

“…IgM and IgG levels in supernatants were determined using a double-sandwich enzyme-linked immunosorbent assay, as described (30 In contrast with these increased proportions, no difference was observed in the absolute counts of CD20+, IgD+, and CD23-t cells between the RA and control groups, but the proportion of lymphocytes in WBC was reduced in RA patients ( P < 0.02) ( Table I). Thus, the increased CD23 expression in RA B cells was not due to an increased number of cells bearing the CD20 or IgD antigens, but to a higher expression of CD23 on their surface.…”