Role of Interleukin-1 in Human B-Cell Activation

Abstract

Mononuclear phagocytes (Mø) play an essential role in both T- and B-cell activation (Unanue, 1972). Thus, Mø have a critical function both as antigen- presenting cells and as cells that provide a focus for effective B- and T-cell collaboration. In addition to activities carried out by means of direct contact between Mø and responding lymphocytes, a number of other functions of Mø appear to be accomplished by secreted factors. The best studied of these factors is Interleukin-1 (IL-1), a Mø-derived factor of 12,000–16,000 daltons that has a variety of amplifying effects both on immunological reactivity and on inflammatory responses in general (Oppenheim and Gery, 1982). While the immunoregulatory role of IL-1 has been well described in a number of murine models of T- and B-cell activation, the function of this molecule in human immune responsiveness has been less well described. The studies presented in this chapter were therefore undertaken, to examine the role of IL-1 in the regulation of antibody production in humans. Specifically, the in vitro generation of immunoglobulinsecreting cells (ISC) triggered by the T-cell-dependent polyclonal B-cell activators, pokeweed mitogen (PWM) and formalinizedStaphylococcus aureus, was used as a model system for dissecting in detail the immunomodulatory potential of IL-1. The data support the conclusion that IL-1 plays a necessary role in the generation of ISC in humans. Moreover, the results indicate that IL-1 delivers a requisite differentiation signal directly to the B-cell, without which subsequent responsiveness to T-cell-derived helper factors and maturation to Ig-secreting cells do not occur.