TGF-beta 1 induces germ-line transcripts of both IgA subclasses in human B lymphocytes

Immunoglobulin (Ig) class switching appears to be preceded by induction of germ-line transcripts. In this report, we demonstrate that transforming growth factor beta (TGF-beta) induces germ-line transcripts of both the IgA subclasses (IgA1 and IgA2) in Branhamella catarrhalis (BC)-activated human spleen B cells. Two germ-line bands, one of approximately 1.85 kb and the other of approximately 1.6 kb, could be seen in cultures treated with TGF-beta. The approximately 1.85 kb band contains mRNA for a germ-line transcript of the membrane form. This band co-migrates with the productive secreted form of alpha mRNA. The other, shorter form of approximately 1.6 kb did not correlate in size with any known form of productive alpha mRNA and contained the secreted form of germ-line alpha mRNA. The induction of alpha germ-line transcripts was accompanied by a concomitant suppression of mu and gamma mRNA. We have also identified the location of a putative I alpha sequence (designated according to the generally accepted nomenclature) within approximately 0.5 kb upstream to the switch alpha (S alpha) region. The relative proportions of IgA-subclass-specific mRNA in TGF-beta-stimulated spleen B cells are concordant with the distribution pattern seen in pokeweed mitogen (PWM)-stimulated spleen mononuclear cells (MNC), which was 89 and 11% for the IgA1 and the IgA2 mRNA respectively. These results suggest a role of TGF-beta in regulating IgA class switching in human B lymphocytes.