Heavy chain-specific suppression of immunoglobulin synthesis and secretion by lymphocytes from patients with selective IgA deficiency

A simple, solid-state immunofluorescent assay specific for the heavy chain of human immunoglobulins (Ig) was adapted for studying pokeweed mitogen (PWM) stimulated Ig biosynthesis and secretion by peripheral blood lymphocytes (PBL) in vitro. PBL from patients with panhypogammaglobulinemia were noted to synthesize and secrete decreased amounts of all classes of immunoglobulin after polyclonal activation of B cells in vitro with PWM. PBL from 14 patients with selective deficiency of IgA were capable of synthesizing and secreting significant levels of IgG and IgM after culture with PWM; however, they did not produce appreciable amounts of IgA. Thus, B lymphocyte differentiation in vitro parallels the clinical status. Several different immunoregulatory phenomena were observed when PBL from patients with selective IgA deficiency were co-cultivated with cells from healthy donors. Most notable was the specific suppression of IgA synthesis and secretion seen in 8 of 14 patients studied, although other modulatory effects including enhancement and suppression of all Ig classes were also observed. These results suggest that the pathologic basis of selective IgA deficiency may be heterogeneous and support a model for the role of Ig class-specific suppressor cells in the pathogenesis of some cases of selective IgA deficiency.