We studied B-lymphocyte function in 12 homosexual male patients with the acquired immunodeficiency syndrome, 5 healthy homosexual men, and 12 heterosexual controls. In comparison with the heterosexual controls, the patients were found to have elevated numbers of cells spontaneously secreting immunoglobulin, decreased B-cell proliferative responses to T-cell-independent B-cell mitogens, and qualitatively deficient helper T cells. The hyperactive spontaneous B-cell responses as well as the refractoriness to signals for T-cell-independent B-cell activation were highly suggestive of an in vivo polyclonal activation of B cells and may have been responsible for the manifestations of B-cell hyperreactivity, such as hypergammaglobulinemia, seen in these patients. We conclude that the scope of immune dysfunction in the acquired immunodeficiency syndrome involves B cells as well as T cells.

The immune responses of 16 patients with nonneoplastic immune mediated diseases including Wegener's granulomatosis, systemic necrotizing vasculitis, cutaneous vasculitis, and relapsing nodular panniculitis were evaluated before and during therapy with chronic low-dose (2 mg/kg/day) cyclophosphamide. A striking selective suppression of B cell function was noted as measured by PWM-induced immunoglobulin secretion. This suppression was a direct effect on the B cells themselves because T cell function, measured by blastogenic responses to the mitogens PHA, Con A, and PWM, was not significantly suppressed. Furthermore, the ability of T cells from cyclophosphamide-treated patients to provide helper function in T cell-dependent B cell assays remained intact. Treated patients manifested a total lymphocytopenia without a selective depletion of relative proportions of B cells or T cell subsets. However, the spontaneous secretion of immunoglobulin by peripheral blood B cells that is elevated in untreated patients was suppressed back to normal levels during cyclophosphamide therapy. This selective effect on spontaneous and induced secretion of immunoglobulin by human B cells may help explain the efficacy of cyclophosphamide therapy in certain antibody and immune complex-mediated diseases.

The modulation of immunoglobulin (Ig) secretion of human peripheral blood mononuclear cells by in vitro hydrocortisone (HC) was evaluated. A marked enhancement of Ig secretion was observed in unstimulated cultures in the presence of HC as compared to cultures without HC. The augmented response was not due to a direct induction of Ig secretion by HC, but resulted from an enhancement or unveiling of the background mitogenic signal provided by the supplemental serum used in culture. HC-induced augmentation of Ig secretion was only seen in unstimulated cultures performed in fetal calf serum (FCS) which is known to possess mitogenic properties. In contrast, HC had no significant effect on Ig secretion of cultures performed in human serum, which provides little or no background mitogenic signal. On the other hand, no enhancement of Ig secretion by HC was seen in cultures maximally stimulated with pokeweed mitogen regardless of whether FCS or human A serum was used. The mechanisms of this modulation of Ig secretion are unclear at present and may include a synergy between corticosteroids and background mitogenic signals (such as FCS) indirectly triggering B cells and/or the dampening of a negative immunoregulatory effect of an accessory cell.

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