Transforming growth factor-beta directs IgA switching in human B cells
van Vlasselaer, P.; Punnonen, J.; de Vries, J.E.
Journal of Immunology 148(7): 2062-2067
1992
ISSN/ISBN: 0022-1767 PMID: 1347548 Document Number: 390070
Transforming growth factor (TGF)-.beta. added to cultures of highly purified human splenic B cells induced high leels of IgA synthesis in the presence of PWM and activated cloned CD4+ T cells. TGF-.beta. had no effect on IgM or IgG production. The induction of IgA synthesis by TGF-.beta. reflected IgA switching, because a strong induction of IgA production was also observed, when sIgA- B cells were cocultured with cloned activated CD4+ T cells in the presence of pokeweed mitogen. Resting CD4+ T cell clones or activated CD8+, TCR-.gamma.delta.+ CD4-,CD8- T cell clones failed to provide the co-stimulatory signal that in addition to TGF-.beta. and pokeweed mitogen was required for induction of IgA switching and IgA synthesis. mAb against CD4 or class II MHC molecules inhibited TGF-.beta. induced IgA synthesis, indicating that CD4-class II MHC interactions are required for productive T-B cell contacts resulting in IgA production. In contrast, anti-LFA-1, anti-CD2, and anti-class I MHC mAB were ineffective. TGF-.beta. failed to induce IgA synthesis by sIgA+ B cells under these culture conditions. Interestingly, induction of IgA production by sIgA- B cells required neutralization of TGF-.beta. activity by addition of the anti-TGF-.beta. mAb 1D11.1G 24 h after onset of the cultures. IgA production was prevented when the anti-TGF-.beta. mAb was added at the start of the cultures, indicating the specificity of the reaction. IgA synthesis was completely suppressed when TGF-.beta. was present during the total culture period of 11 days. These findings indicate that TGF-.beta. can act as a specific switch factor for IgA, provided it is only present at early stages of the cultures.