TGF-BETA-1 INDUCES GERM-LINE TRANSCRIPTS OF BOTH IGA SUBCLASSES IN HUMAN LYMPHOCYTES-B

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.