The role of monocytes in pokeweed mitogen-stimulated human B cell activation: separate requirements for intact monocytes and a soluble monocyte factor

Mononuclear phagocytes (M phi) play an essential role in mitogen-induced proliferation and generation of immunoglobulin-secreting cells (ISC) from human peripheral blood lymphocytes. The nature of this accessory function was examined using the pokeweed mitogen (PWM) model of lymphocyte activation. M phi-depleted human peripheral blood lymphocytes are unresponsive to PWM. Fresh, intact M phi, but not heat-killed M phi, reconstitute the capacity of these cells both to proliferate and generate ISC in response to PWM. In the presence of intact M phi, soluble M phi factors augment PWM-induced generation of ISC but do not enhance 3H-thymidine incorporation. In the absence of intact M phi, the M phi supernatants are unable to support either response. Secretion of active M phi supernatants was completed within the first 24 to 48 hr of incubation, with little additional factor secreted thereafter. Aged M phi, which no longer secreted active factors, fully reconstituted the proliferative response of M phi-depleted lymphocytes; however, they were unable to support PWM-triggered differentiation of B cells into ISC. The addition of active M phi supernatants to the aged M phi restored their capacity to support PWM-triggered generation of ISC. Highly purified Interleukin 1 was also able to enhance the accessory cell function of both fresh and aged M phi in a similar manner. These results suggest that IL-1 is the M phi factor required for the differentiation of human B cells into ISC. Moreover, the data indicate that in the human, M phi accessory cell function involves 2 separate modalities. Both intact M phi and a factor released by fresh M phi (Interleukin 1) are required to support differentiation of B cells into ISC, while only intact M phi are necessary for PWM-induced lymphocyte proliferation.