Effect of pure bovine brain-derived gangliosides on normal human B cell proliferation in vitro

Pure gangliosides obtained from bovine brain including GM1, GD1b, GT1b and asialo-GM1 (GA1) did not induce normal human B cell proliferation in vitro. No B cell proliferation was observed either when GM1 was tested in the presence of interleukin-2 (IL-2), IL-4 or IL-6. Furthermore, the proliferative responses of human B cells induced by Staphylococcus aureus Cowan I (SAC), a T cell-independent B cell mitogen, were inhibited by these gangliosides. The degree of inhibition was influenced by ganglioside-bound sialic acid, although sialic acid per se was not inhibitory. Strongest inhibition was observed in the presence of GT1b (EC50 8.8 microM/10(5) B cells) and lowest in the presence of GA1 (EC50 129.5 microM/10(5) B cells) with intermediate values for GM1 and GD1b. GM1 inhibition of SAC-induced B cell proliferation did not represent cytotoxic effects and was still evident when GM1 was added 24-48 h after the beginning of the cultures. GM1 inhibition of SAC-induced proliferation was not reversed by the addition of IL-2, IL-4, IL-6 or their combination. In addition, GM1 inhibited the ILs-driven proliferative responses of SAC-induced B cell blasts. However, no inhibition of Epstein-Barr virus-induced B cell proliferative responses was observed. In conclusion, these results show that bovine brain-derived gangliosides do not induce proliferative responses of normal human B cells but, on the contrary, inhibit B cell responses induced by SAC.