Studies of the pathogenesis of angioimmunoblastic lymphadenopathy

We studied the immune functions of two patients with angioimmunoblastic lymphadenopathy (AILD) in an attempt to determine whether the B cells were primarily hyperactive or, rather, if T cell abnormalities might underlie the B cell hyperactivity observed in these patients. We found that the B cells of the AILD patients did not proliferate spontaneously, nor were they induced to proliferate excessively by fresh normal T cells. In contrast, AILD T cells induced both autologous and allogeneic B cells to proliferate and to differentiate into Ig secreting cells. Spontaneous culture supernates of T cells obtained from each patient induced substantial proliferation of B cells (B cell-activating activity) as well as proliferation in a standard costimulatory assay (B cell growth factor activity). The culture supernate of a T cell line, which was established from one patient, showed both activities. The T cell line supernate also induced Ig production by staphylococcal A Cowan-activated B cells. None of these properties of AILD T cells was found among 10 normal controls. The addition of AILD T cells to autologous or allogeneic B cells in the presence of pokeweed mitogen (PWM) led to marked suppression of both proliferation and Ig production. This was true even in the presence of fresh normal T cells. Pretreatment studies showed that suppressor cells were induced by the interaction of AILD T cells with PWM-activated B cells. The present study suggests that the B cell hyperactivity observed in AILD patients might in part be due to excessive T cell effects on B cells. In addition, our results may help clarify the paradoxical impaired responsiveness to in vitro stimulation with PWM by active B cells from patients with autoimmune diseases.