Differentiation of cord blood lymphocytes into IgA-producing cells in response to breast milk stimulatory factor

Abstract

Although B cells with IgA, IgG, and IgM surface immune globulins are identified in the peripheral blood by 14 weeks gestation, only IgM differentiation has been noted when cord blood lymphocytes (CBL) were studied in vitro. These data suggest that CBL differentiation may be a regulated process. To investigate this possibility, CBLs were incubated with both pokeweed mitogen (PWM) and an IgA-specific stimulatory factor produced in culture by breast milk cells. Further, to roughly determine the molecular size of this milk cell factor, adult peripheral blood lymphocytes (PBL) were incubated with factor preparations which had been filtered to remove all proteins greater than 50,000 molecular weight. The release of IgA, IgG, and IgM by the lymphocytes in culture was quantitated using double-antibody (Ab) competitive radioimmunoassays. The milk cell factor stimulated IgA synthesis in 15 21 CBL cultures with a median IgA production of 400 ng above that measured in the unstimulated control cultures ( P < 0.001). PWM did not stimulate IgA synthesis and had minimal effect on IgG or IgM production by CBLs. In contrast, PWM stimulated a significant increase ( P < 0.001) in IgA, IgG, and IgM synthesis by PBLs. Finally, unfiltered milk cell preparations induced a significant ( P < 0.02) increase in IgA synthesis by PBLs which was abolished following removal of proteins having a molecular weight greater than 50,000. Therefore, it is postulated (1) that CBLs are capable of differentiating into immunoglobulin-producing plasma cells, (2) that CBLs differentiate in response to appropriate immunoglobulin class-specific stimuli, (3) that CBLs are unresponsive to PWM, and (4) that the soluble mediator of immunologic regulation released by human milk cells has a molecular weight greater than 50,000.