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Human recombinant interleukin-4 (rIL-4) was assessed for its ability to promote the proliferative response of purified human B cells co-stimulated with submitogenic concentrations of soluble F(ab′)2 fragments of anti-immunoglobulin (Ig) antibodies. The growth-promoting activity of rIL-4 was usually as potent as, or even more potent than, that of recombinant interlcukin-2 (rIL-2), and more potent than that of recombinant interferon-gamma (rIFN-γ). Preincubation with rIL-4 did not cause enhancement of the proliferative response of B cells to the subsequent addition of rIL-4 and anti-IgM antibody. In contrast, the proliferative response of B cells preincubated with anti-IgM antibody and rIL-4 was potentiated by the subsequent addition of rIL-4. The simultaneous addition of rIFN-γ and rIL-2 or rIFN-γ, and rIL-4 had an additive effect in comparison with the response induced by rIL-2 or rIL-4 alone, respectively, whereas simultaneous addition of rIL-2 and rIL-4 induced a response equal or lower than that stimulated by rIL-2 or rIL-4 alone. The addition of rIFN-γ at the beginning of culture or preincubation of B cells with rIFN-γ and anti-IgM antibody potentiated the proliferative response of B cells to the subsequent addition of either rIL-2 or rIL-4. Taken together, these data suggest that rIL-4 acts as a growth factor for activated human B cells and displays on such cells a growth-promoting activity similar to that of rIL-2. [ABSTRACT FROM AUTHOR]

Recombinant interleukin-2 (rIL-2) induced highly purified human tonsillar B cells to differentiate into immunoglobulin (Ig)-producing cells in vitro. The B-cell response was not due to rIL-2- contaminating substances, but reflected the activity of IL-2 itself, since it was inhibited by addition to the cultures of anti-TAC monoclonal antibody. The rIL-2-induced B-cell response was apparently not mediated by factors released by residual T cells present in B-cell suspensions at undetectable levels, since supernatants (SN) from unstimulated autologous T cells cultured at concentrations even much higher than those possibly contaminating B-cell suspensions did not induce any detectable Ig production. In addition, the Ig production by B cells cultured with SN prepared from high numbers of autologous T cells stimulated with rIL-2, as well as from allo-activated or mitogen-stimulated T cells, was of the same magnitude as the Ig production resulting from direct addition of rIL-2 concentrations comparable with those present in the supernatants. After centrifugation on Percoll density gradients, most of the tonsillar B cells responsive to rIL-2 were recovered in the lower density cell fraction containing a number of larger activated B cells. Moreover, B-cell enriched suspensions from peripheral blood (PB) (which usually contains a lower number of in vivo activated B cells than tonsil) showed poor or no response to rIL-2 alone, but displayed significant Ig production when rIL-2 was added to the cultures in the presence of Staphylococcus aureus Cowan I (SAC) bacteria. Taken together, these data indicate that IL-2 can directly induce differentiation into Ig-producing cells of in vivo or in vitro activated human B cells. [ABSTRACT FROM AUTHOR]

The nature of lymphocyte subsets activated by soluble and insoluble protein A (SpA) was investigated by testing the ability of human tonsil populations to form rosettes with human red blood cells coated with SpA (SpA-HRBC) and to respond in vitro to SpA. SpA coupled to Sepharose beads (SpA-Seph) and Staphylococcus aureus strain Cowan I (StaCw). Purified human I cells, which were unable to form rosettes with SpA-HRBC, were not activated by SpA-Seph or StaCw, whereas 8-cell enriched suspensions, where the number of lymphocytes forming rosettes with SpA-HRBC was significantly increased in comparison with that found in unfractionated populations, showed DNA synthesis equal to or greater than unseparated lymphocytes. In contrast, soluble SpA was unable to activate highly purified B lymphocytes in 3 day cultures and induced higher DNA synthesis in unseparated than in purified human T cells. Tonsil cell suspensions depleted in cells forming rosettes with SpA-I-IRBC synthesized significantly less DNA in the presence of SpA-Seph and lost the ability to respond to StaCw. The depletion in either IgG-bearing or IgM- and/or IgD-bearing cells induced a reduction in the response of lymphocytes to SpA-Seph and StaCw. Depletion in IgM- and/or IgD-bearing cells induced a more marked decrease in the response to StaCw than depletion in lgG-bearing lymphocytes, while the decrease of the response to SpA-Seph, induced by depletion in IgM- and/or IgD-bearing cells, was lower than that induced by depletion in lgG-bearing lymphocytes. In contrast, soluble SpA-induced proliferation was not significantly affected by depletion of cells forming rosettes with SpA-HRBC' or of IgG-bearing or IgM- and/or IgD-bearing lymphocytes. These results suggest that the mitogenicity of SpA-Seph and StaCw is due to a selective binding of insoluble SpA to components present on the membrane of either IgO- bearing or IgM- and/or IgD-bearing lymphocytes. They also indicate that the potentiation of T-cell response to soluble SpA, induced by the presence in culture of non-T cells, is not due to B lymphocytes which are able to form ,rosettes with SpA-HRBC and to respond to SpA itself when it is presented to the cells on an insoluble matrix. [ABSTRACT FROM AUTHOR]