Platelet Activating Factor Inhibits Both the Proliferation and the Differentiation of Activated B Lymphocytes in Response to Interleukin-2

Abstract

The role of the platelet activating factor in human B lymphocyte responses to Interleukin-2 was examined and compared with that of Interleukin-4 by assessing the ability of this molecule to modulate proliferation and differentiation. Highly purified B lymphocytes were prestimulated for 48 h with Staphylococcus aureus Cowan Strain I and then were cultured with Interleukin-2 alone or in combination with either Interleukin-4 or the platelet activating factor and the proliferation (after 3 days) and the immunoglobulins (IgG and IgM) production (after 7 days) were evaluated. When SAC-activated B lymphocytes were preincubated overnight with PAF (0.0001 to 1 μM) or with IL-4 (1 to 100 U/ml) both the IL-2-induced proliferation and immunoglobulins secretion were inhibited. This inhibition was not a reflection of a decreased expression of the IL-2 receptor (CD25) because this expression was not modified on SAC-activated B lymphocytes after preincubation with either PAF or IL-4. Moreover, this suppression effect was not the result of a delayed response to IL-2.

The PAF-induced suppression was overcome in the presence of PAF antagonists (BN 52021 and BN 50730) but was not modified in the presence of a neutralizing anti-IL-4 antiserum. On the other hand, the IL-4 mediated suppression was totally reversed in the presence of the neutralizing anti-serum and only marginally reversed in the presence of the PAF antagonists. These results indicate that both PAF and IL-4 may exert a number of immunoregulatory actions on human B lymphocyte proliferation and differentiation. They interfere with the stimulation of activated B lymphocytes by IL-2 and could play an important immunoregulatory role in the determination of isotypic regulation in the specific humoral responses.