ヒトB細胞活性化機序に関する研究 : V.Ia様抗原およびT細胞分化抗原がPokeweed MitogenによるB細胞の活性化過程に果たす役割

抄録

We have first asked if interactions between T-B cells are necessary to activate human B cells when stimulated with polyclonal B cell activators, pokeweed mitogen (PWM) and Staphylococcus aureus Cowan I strain (SAC). When the cultures of B cells, T cells and monocytes were stimulated by either PWM or SAC, both stimulants could activate the B cells to secrete immunoglobulin (Ig). Moreover, when T cells were replaced by T cell-derived soluble factors, B cell-stimulating factors (BSF), SAC-stimulated, but not PWM-stimulated, B cells could differentiate into Ig-secreting cells. These results suggest that 1) B cells can be directly activated by SAC without T-B cell interactions to become sensitive to BSF, and that 2) the cellular interactions can be involved in the activation of B cells by PWM. A question has been raised from the above data as to whether the T-B cell interactions for the whole period of culture are needed to activate B cells by PWM. To adress this question, PWM-stimulated cultures of T and B cells and monocytes were harvested at various culture periods (1st-step cultures), B cells isolated, and those B cells were further incubated for 5 days with BSF (2nd-step cultures). The B cells from 1st-step culture incubated for more than 6 hours could proliferate and differentiate adequately in response to BSF. Addition of either T cell subset, T4^+ or T8^+ cells to 1st-step cultures of PWM-stimulated B cells demonstrated that interactions of B cells with T4^+, but not T8^+, cells are necessary for the B cell activation. Moreover, when either anti-Ia or anti-T4 antibody was introduced into the 1st-step cultures, B cells could not be activated by PWM to become sensitive to BSF in the 2nd-step cultures. In contrast, anti-T3 or anti-T8 antibody did not appear to exert any effects on the PWM-induced activation of B cells. We have next examined whether these monoclonal antibodies can modulate responsiveness of B cells that have been already activated by PWM in the 1st-step cultures and isolated from such the cultures to BSF in 2nd-step cultures. Addition of either monoclonal antibody to the 2nd-step cultures could not accelarate nor inhibit the ability of the B cells to proliferate and produce Ig in the 2nd-step cultures. The data presented in this paper suggest that SAC can activate B cells by themselves, and SAC stimulation does not require interactions with T cells, that recognitive interactions between Ia-like antigens on B cells and T4 antigens on T4^+ cells are essential for B cell activation by PWM, and that once those cells are activated by SAC or PWM, they will proliferate, differentiate and secrete Ig under the influence of BSF.