Transforming growth factor-beta directs IgA switching in human B cells.
Transforming growth factor (TGF)-beta added to cultures of highly purified human splenic B cells induced high levels 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.
van Vlasselaer
P
P
DNAX Research Institute, Palo Alto, CA 94304-1104.
Punnonen
J
J
de Vries
J E
JE
D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015704:CD4 Antigens / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D002478:Cells, Cultured; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis*; D007132:Immunoglobulin Isotypes / Q000032:analysis; D011947:Receptors, Antigen, B-Cell / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D007070:Immunoglobulin A; D007132:Immunoglobulin Isotypes; D011947:Receptors, Antigen, B-Cell; D016212:Transforming Growth Factor beta